Condensed heterocylic compounds and herbicides containing them as active ingredients

Abstract

Condensed heterocyclic compounds of the general formula: 1

Description

TECHNICAL FIELD

[0001] The present invention relates to condensed heterocyclic compounds and their use.

DISCLOSURE OF INVENTION

[0002] The present inventors have extensively studied to find compounds having excellent herbicidal activity. As a result, they have found that the condensed heterocyclic compounds of general formula I as depicted below have excellent herbicidal activity, thereby completing the present invention.

[0003] The present invention provides condensed heterocyclic compounds of general formula I: 2

[0004] (hereinafter referred to as the present compounds)

[0005] wherein T is carbon or nitrogen; when T is carbon, then the bond between T and A is a double bond, the bond between A and Y is a single bond, and Y is oxygen, sulfur, or N—R142; or when T is nitrogen, then the bond between T and A is a single bond, the bond between A and Y is a double bond, and Y is nitrogen or C—R152;

[0006] wherein R142 is hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, cyano, —COR143, —N(R145)R146, or —N═C(R147)R148; R152 is hydrogen, halogen, C1-C3 alkyl, nitro, amino, cyano, or —COR153;

[0007] wherein R143 is hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, hydroxyl, C1-C5 alkoxy, or —N(R156)N157; R145 and R146 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, formyl, (C1-C5 alkyl)carbonyl, (C1-C5 haloalkyl)carbonyl, or (C1-C5 alkoxy)carbonyl; R147 and R148 are independently hydrogen or C1-C5 alkyl; R15 is hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, hydroxyl, C1-C5 alkoxy, or —N(R154)R155;

[0008] wherein R156 and R157 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, formyl, (C1-C5 alkyl)carbonyl, (C1-C5 haloalkyl)carbonyl, or (C1-C5 alkoxy)carbonyl; R154 and R155 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, (C1-C5 alkoxy)carbonyl, formyl, (C1-C5 alkyl)carbonyl, or (C1-C5 haloalkyl)carbonyl;

[0009] A is nitrogen or C—R141 wherein R141 is hydrogen, halogen, or C1-C3, alkyl;

[0010] R1 is hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, hydroxymethyl, nitro, or cyano;

[0011] R2 is hydrogen, halogen, C1-C11 alkyl, C1-C11 haloalkyl, hydroxymethyl, nitro, cyano, —N(R9)R10, —OR11, —SR12, —SO2R13, —COX, —COOR14, —CON—(R15)R16, —COR17, —C(R26)═NOR19, —C(R27)═C(R21)R22, or —CH(R23)—CH(R24)R25;

[0012] R3 is hydrogen, halogen, C1-C11 alkyl, C1-C11 haloalkyl, hydroxymethyl, nitro, cyano, —N(R59)R60, —OR61, —SR62, —SO2R63, —COX, —COOR64, —CO—N(R65)R66, —COR67, —C(R76)═NOR69, —C(R77)═C(R71)R72, or —CH(R73)—CH(R74)R75;

[0013] R4 is hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, hydroxymethyl, nitro, or cyano;

[0014] wherein X is chlorine or bromine;

[0015] R9 and R59 are independently hydrogen, C1-C5 alkyl, (C1-C5 alkyl)-carbonyl, or (C1-C5 alkoxy)carbonyl;

[0016] R10, R11, and R12 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C3-C10 halocycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C3-C10 alkenyl, C3-C10 haloalkenyl, C3-C10 alkynyl, C3-C10 haloalkynyl, cyano C1-C6 alkyl, (C1-C5 alkyl)carbonyl, (C1-C5 haloalkyl)carbonyl, (C3-C10 cycloalkyl)carbonyl, (C1-C5 alkyl)carbonyl C1-C5 alkyl, (C1-C5 haloalkyl)carbonyl C1-C5 alkyl, hydroxy C1-C5 alkyl, C1-C5 alkoxy C1-C5 alkyl, C1-C5 alkylthio C1-C5 alkyl, (C1-C5 alkoxy)carbonyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl, —C(R43)(R44)—C(═O)ON(R45)R46, —C(R47)(R48)—CON(R49)R50, —CH2—C(R56)═N—OR55, —CHMe—C(R56)═NOR57, (C3-C10 alkenoxy)carbonyl C1-C5 alkyl, (C3-C10 alkynoxy)carbonyl C1-C5 alkyl, phenoxycarbonyl, benzyloxycarbonyl, carboxy (C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 alkoxy)carbonyl (C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C3-C10 alkenoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C3-C10alkynoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl, carboxy(C1-C5 alkyl)carbonyl, (C1-C10 alkoxy)carbonyl(C1-C5 alkyl)carbonyl, (C1-C10 haloalkoxy)carbonyl(C1-C5 alkyl)carbonyl, C1-C5 alkylsulfonyl, C1-C5 haloalkylsulfonyl, —SO2N—(R51)R52, —CON(R53)R54, optionally substituted benzyl, or optionally substituted phenyl;

[0017] R60, R61, and R62 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C1-C10 halocycloalkyl, C3-C10cycloalkyl C1-C3 alkyl, C3-C10 alkenyl, C1-C10 haloalkenyl, C3-C10 alkynyl, C3-C10 haloalkynyl, cyano C1-C6 alkyl, (C1-C5 alkyl)carbonyl, (C1-C5 haloalkyl)carbonyl, (C3-C10 cycloalkyl)carbonyl, (C1-C5 alkyl)carbonyl C1-C5 alkyl, (C1-C5 haloalkyl)carbonyl C1-C5 alkyl, hydroxy C1-C5 alkyl, C1-C5 alkoxy C1-C5 alkyl, C1-C5 alkylthio C1-C5 alkyl, (C1-C5 alkoxy)carbonyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl, —C(R163)(R164)—C(═O)ON(R165)R166, —C(R167)R168)—CON(R169)R170, —CH2—C—(═NOR175)R176, —CHMe—C(═NOR177)R178, (C3-C10 alkenoxy)carbonyl C1-C5 alkyl, (C3-C10 alkynoxy)carbonyl C1-C5 alkyl, phenoxycarbonyl, benzyloxycarbonyl, carboxy(C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 alkoxy)carbonyl (C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C3-C10 alkenoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C3-C10 alkynoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl, carboxy(C1-C5 alkyl)carbonyl, (C1-C10alkoxy)carbonyl(C1-C5 alkyl)carbonyl, (C1-C1-0haloalkoxy)carbonyl(C1-C5 alkyl)carbonyl, C1-C5 alkylsulfonyl, C1-C5 haloalkylsulfonyl, —SO2N(R171)R172, —CON(R173)R174, optionally substituted benzyl, or optionally substituted phenyl;

[0018] wherein R43, R44, R163, and R164 are independently hydrogen, halogen, C1-C5 alkyl, or C1-C5 haloalkyl;

[0019] R45, R46, R165, and R166 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R45 and R46 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring, or R165 and R166 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring;

[0020] R47, R48, R167, and R168 are independently hydrogen, halogen, C1-C5 alkyl, or C1-C5 haloalkyl;

[0021] R49, R50, R169, and R170 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R49 and R50 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R169 and R170 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

[0022] R51, R52, R171, and R172 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C0-C6 alkynyl; or R51 and R52 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R171 and R172 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

[0023] R53, R54, R173, and R174 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R1 and R54 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R173 and R174 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

[0024] R56, R57, R175, and R177 are independently hydrogen or C1-C3 alkyl;

[0025] R56, R58, R176, and R178 are independently hydrogen, C1-C5 alkyl (C1-C5 alkoxy)carbonyl, (C1-C5 haloalkoxy)carbonyl, (C3-C5 cycloalkoxy)carbonyl, (C3-C5 alkenoxy)carbonyl, or (C3-C5 alkynoxy)carbonyl;

[0026] R13 is hydroxy, chlorine, C1-C10 alkyl, C1-C10 haloalkyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10halocycloalkoxy)carbonyl C1-C5 alkyl, —N(R79)R80, or —OR81;

[0027] R63 hydroxy, chlorine, C1-C10alkyl, C1-C10 haloalkyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl, —N(R179)R180, or —OR181;

[0028] wherein R79 and R179 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl; R80 and R180 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R79 and R80 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- or 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R179 and R180 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- or 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; and R81 and R181 are independently C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10cycloalkoxy)carbonyl C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl;

[0029] R14 is hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C1-C10 halocycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C3-C10 alkenyl, C3-C10haloalkenyl, C1-C10 alkynyl, C3-C10 haloalkynyl, carboxy C0-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 alkenoxy)carbonyl C1-C5 alkyl, (C3-C10 alkynoxy)carbonyl C1-C5 alkyl, —N(R82)R83, optionally substituted benzyl, or optionally substituted phenyl;

[0030] R64 is hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10cycloalkyl, C3-C10halocycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C3-C10 alkenyl, C3-C10 haloalkenyl, C3-C10 alkynyl, C3-C10 haloalkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10halocycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 alkenoxy)carbonyl C1-C5 alkyl, (C3-C10alkynoxy)carbonyl C1-C5 alkyl, —N(R182)R183, optionally substituted benzyl, or optionally substituted phenyl;

[0031] wherein R82 and R182 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl; R83 and R183 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R82 and R83 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R182 and R183 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

[0032] R15 and R65 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C1-C10cycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C1-C10 alkenyl, C3-C10alkynyl, cyano C1-C6 alkyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, optionally substituted benzyl, or optionally substituted phenyl; R16 and R66 are independently hydrogen, C1-C10 alkyl, or C1-C10 haloalkyl; or R15 and R16 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R65 and R66 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

[0033] R17, R26, R27, R67, R76, and R77 are independently hydrogen, cyano, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10cycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, (C1-C6 alkoxy)carbonyl, or (C1-C6 alkoxy)carbonylmethyl;

[0034] R19 and R69 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C3-C10 halocycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C3-C10 alkenyl, C3-C10 haloalkenyl, C3-C10 alkynyl, C3-C10 haloalkynyl, cyano C1-C6 alkyl, carboxy C1-C5 alkyl, (C1-C10alkoxy)carbonyl C1-C5 alkyl, (C1-C10haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10cycloalkoxy)carbonyl C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl;

[0035] R21 and R71 are independently hydrogen, halogen, C1-C3 alkyl, or C1-C3 haloalkyl;

[0036] R22 and R25 are independently carboxy, (C1-C10 alkoxy)carbonyl, (C1-C10 haloalkoxy)carbonyl, (C3-C10 cycloalkoxy)carbonyl, (C1-C10 halocycloalkoxy)carbonyl, carboxy(C1-C5 alkoxy)carbonyl, (C1-C10 alkoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C1-C10 haloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10 cycloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10 alkenoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10 alkynoxy)carbonyl (C1-C5 alkoxy)carbonyl, —CON(R84)R85, or —C(═O)ON(R86)R87;

[0037] R72 and R75 are independently carboxy, (C1-C10 alkoxy)carbonyl, (C1-C10haloalkoxy)carbonyl, (C3-C10 cycloalkoxy)carbonyl, (C3-C10halocycloalkoxy)carbonyl, carboxy(C1-C5 alkoxy)carbonyl, (C1-C10 alkoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C1-C10 haloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10cycloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10alkenoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10 alkynoxy)carbonyl (C1-C5 alkoxy)carbonyl, —CON(R184)R185, or —C(═O)ON(R186)R187;

[0038] wherein R84 and R184 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C5 alkenyl, C3-C6 alkynyl, carboxy C1-C5 alkyl, (C1-C10alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl; R85 and R185 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R84 and R85 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R184 and R185 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

[0039] R86 and R186 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 Cycloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl; R87 and R187 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C1-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R86 and R87 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring; or R186 and R187 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring;

[0040] R23, R , R73, and R74 are independently hydrogen, halogen, C1-C3 alkyl, or C1-C3 haloalkyl; and

[0041] Q is any one group of Q1 to Q23 of the general formula: 3 4 5

[0042] wherein:

[0043] in Q1, E1 and E2 are independently C1-C6 alkyl optionally substituted with halogen, or C3-C6 cycloalkyl optionally substituted with halogen; or E1 and E2 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring (which unsaturated ring includes no aromatic rings), and the ring may optionally be substituted with methyl or halogen;

[0044] in Q2, E3 and E4 are independently C1-C6 alkyl optionally substituted with halogen, or C3-C6 cycloalkyl optionally substituted with halogen; or E3 and E4 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen; D1 and D2 are independently oxygen or sulfur; and Z1 is nitrogen or CH;

[0045] in Q3, E5 is hydrogen or C1-C6 alkyl optionally substituted with halogen; and D3 is oxygen or sulfur;

[0046] in Q4, E6 and E7 are independently hydrogen, C1-C6 alkyl optionally substituted with halogen, or C3-C6 cycloalkyl optionally substituted with halogen; or E6 and E7 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen;

[0047] in Q5, E8 and E9 are independently hydrogen, C1-C6 alkyl optionally substituted with halogen, or C3-C6 cycloalkyl optionally substituted with halogen; or E8 and E9 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen;

[0048] in Q6, E10 is hydrogen, C1-C6 alkyl optionally substituted with halogen, or C1-C3 alkoxy optionally substituted with halogen; E11 is hydrogen or C1-C6 alkyl optionally substituted with halogen; or E10 and E11 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring (which unsaturated ring includes no aromatic rings), and the ring may optionally be substituted with methyl or halogen; and E44 is halogen or C1-C3 alkyl;

[0049] in Q7, E12 is C1-C6 alkyl optionally substituted with halogen; and D4 is oxygen or sulfur;

[0050] in Q8, E13 is C1-C6 alkyl optionally substituted with halogen; and E14 is hydrogen or halogen;

[0051] in Q9, E15 is hydrogen or C1-C6 alkyl; E16 is C1-C6 alkyl optionally substituted with halogen; or E15 and E16 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring (which unsaturated ring includes no aromatic rings), and the ring may optionally be substituted with methyl or halogen;

[0052] in Q10, E17, E18, and E19 are independently hydrogen or C1-C6 alkyl; and D5 is oxygen or sulfur;

[0053] in Q11, E20 and E21 are independently hydrogen or C1-C6 alkyl; and D6 is oxygen or sulfur;

[0054] in Q12, E22 and E23 are independently hydrogen or C1-C6 alkyl;

[0055] in Q13, E24 is hydrogen or C1-C3 alkyl;

[0056] in Q14, E25 is hydrogen, C1-C3 alkyl, or halogen; E26 is C1-C3 alkyl optionally substituted with halogen; E27 is hydrogen, amino, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, or optionally substituted benzyl; and D7 is oxygen or sulfur;

[0057] in Q15, E28 is C1-C3 alkyl optionally substituted with halogen; E29 is hydrogen, amino, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, or optionally substituted benzyl; and D8 is oxygen or sulfur;

[0058] in Q16, E30 is C1-C3 alkyl optionally substituted with halogen, E31 is hydrogen or C1-C3 alkyl optionally substituted with halogen; or E30 and E31 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring (which unsaturated ring includes no aromatic rings), and the ring may optionally be substituted with methyl or halogen; and E42 is hydrogen or C1-C3 alkyl optionally substituted with halogen;

[0059] in Q17, E32 is C1-C3 alkyl optionally substituted with halogen; E33 is hydrogen, halogen, amino, C1-C3 alkyl optionally substituted with halogen, C1-C3 alkoxy optionally substituted with halogen, or C1-C3 alkylthio optionally substituted with halogen; and E43 is hydrogen or C1-C3 alkyl optionally substituted with halogen;

[0060] in Q18, E34 is C1-C3 alkyl optionally substituted with halogen;

[0061] in Q19, D9 is oxygen or sulfur; and V1 is —CH2—, —CH2—CH2—, or —CH2—CH2—CH2—;

[0062] in Q20, E35 is C1-C3 alkyl optionally substituted with halogen; Z2 is nitrogen or CH; and V2 is —CH2—CH2—, —CH═CH—, —N═CH—, —CH═N—, or —N═N—;

[0063] in Q21, E36 and E37 are independently C1-C6 alkyl; or E36 and E37 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen; D10 and D11 are independently oxygen or sulfur; and Z3 is nitrogen or CH;

[0064] in Q22, E38 is hydrogen or C1-C6 alkyl; E39 is C1-C3 alkyl optionally substituted with halogen; or E38 and E39 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen; and D12 is oxygen or sulfur; and

[0065] in Q23, E40 is hydrogen or C1-C6 alkyl; E41 is C1-C3 alkyl, or C3-C6 cycloalkyl; or E40 and E41 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen; and D13 is oxygen or sulfur.

[0066] The present invention further provides herbicides containing them as active ingredients, and condensed heterocyclic compounds of general formula II: 6

[0067] wherein A1 is C—R31 and Y11 is oxygen, sulfur, or N—R32; wherein R31 is nitro, amino, cyano, carboxyl, or (C1-C3 alkoxy)carbonyl, and R32 is hydrogen, C1-C5 alkyl, C3-C8 alkenyl, or C3-C6 alkynyl; and Q, R1, R2, R3, and R4 are as defined above, which heterocyclic compounds are useful as intermediates for the production of the present compounds.

MODE FOR CARRYING OUT THE INVENTION

[0068] For the groups represented by R142, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C3-C6 alkenyl may include allyl and 1-methylpropenyl; and C3-C6 alkynyl may include propargyl and 1-methylpropynyl.

[0069] For the groups represented by R143, C1-C3 alkyl may include methyl, ethyl, propyl, and isopropyl; C1-C3 haloalkyl may include trifluoromethyl and difluoromethyl; and C1-C5 alkoxy may include methoxy, ethoxy, propoxy, and isopropoxy.

[0070] For the groups represented by R145 or R146, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; (C1-C5 alkyl)carbonyl may include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, and butylcarbonyl; (C1-C5 haloalkyl)carbonyl may include trifluoroacetyl, difluoroacetyl, chlorodifluoroacetyl, and dichloroacetyl; and (C1-C5 alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, and isopropoxycarbonyl.

[0071] For the groups represented by R147 or R148, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl.

[0072] For the elements or groups represented by R152, halogen may include fluorine, chlorine, bromine, and iodine; and C1-C3 alkyl may include methyl, ethyl, propyl, and isopropyl.

[0073] For the groups represented by R153, C1-C3 alkyl may include methyl, ethyl, propyl, and isopropyl; C1-C3 haloalkyl may include trifluoromethyl and difluoromethyl; and C1-C5 alkoxy may include methoxy, ethoxy, propoxy, and isopropoxy.

[0074] For the groups represented by R156 or R157, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; (C1-C5 alkyl)carbonyl may include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, and butylcarbonyl; (C1-C5 haloalkyl)carbonyl may include trifluoroacetyl, difluoroacetyl, chlorodifluoroacetyl, and dichloroacetyl; and (C1-C5 alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, and isopropoxycarbonyl.

[0075] For the groups represented by R154 or R155, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; (C1-C5 alkyl)carbonyl may include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, and butylcarbonyl; (C1-C5 haloalkyl)carbonyl may include trifluoroacetyl, difluoroacetyl, chlorodifluoroacetyl, and dichloroacetyl; and (C1-C5 alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, and isopropoxycarbonyl.

[0076] For the groups or elements represented by R141, C1-C3 alkyl may include methyl, ethyl, and isopropyl; and halogen may include fluorine, chlorine, bromine, and iodine.

[0077] For groups represented by R31, (C1-C3 alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, and isopropoxycarbonyl.

[0078] For the groups represented by R32, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C3-C6 alkenyl may include allyl and 1-methylpropenyl; and C3-C6 alkynyl may include propargyl and 1-methylpropynyl.

[0079] For the elements or groups-represented by R1, halogen may include fluorine, chlorine, bromine, and iodine; C1-C3 alkyl may include methyl and ethyl; and C1-C3 haloalkyl may include trifluoromethyl and difluoromethyl.

[0080] For the elements or groups represented by R2 or R3, halogen may include fluorine, chlorine, bromine, and iodine; C1-C11 alkyl may include methyl, ethyl, and isopropyl; and C1-C11 haloalkyl may include trichloromethyl, trifluoromethyl, chlorodifluoromethyl, difluoromethyl, pentafluoroethyl, and 1,1-difluoroethyl.

[0081] For the elements or groups represented by R4, halogen may include fluorine, chlorine, bromine, and iodine; C1-C3 alkyl may include methyl and ethyl; and C1-C3 haloalkyl may include trifluoromethyl and difluoromethyl.

[0082] For the groups represented by R9 or R59, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl (wherein “t” means “tertiary”; this also holds below), and isoamyl; (C1-C5 alkyl)carbonyl may include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, and butylcarbonyl; and (C1-C5 alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, and t-butoxycarbonyl.

[0083] For the groups represented by R10, R11, R12, R60, R61, or R62, C1-C10 alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; C1-C10 haloalkyl may include 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifluoroethyl; C3-C10cycloalkyl may include cyclopentyl and cyclohexyl; C3-C10halocycloalkyl may include 4,4,-difluorocyclopentyl and 3-chlorocyclohexyl; C3-C10cycloalkyl C1-C3 alkyl may include cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl; C3-C10 alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C3-C10 haloalkenyl may include 2-chloro-2-propenyl and 3,3-dichloro-2-propenyl; C1-C10 alkynyl may include propargyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, and 1,1-dimethyl-2-propynyl; C3-C10 haloalkynyl may include 3-iodo-2-propynyl and 3-bromo-2-propynyl; cyano C1-C6 alkyl may include cyanomethyl and cyanoethyl; (C1-C5 alkyl)carbonyl may include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, and butylcarbonyl; (C1-C5 haloalkyl)carbonyl may include trifluoroacetyl, difluoroacetyl, chlorodifluoroacetyl, and dichloroacetyl; (C3-C10cycloalkyl)carbonyl may include cyclopropylcarbonyl and cyclopentylcarbonyl; (C1-C5 alkyl)carbonyl C1-C5 alkyl may include 2-oxopropyl, 3-methyl-2-oxobutyl, and 3-oxopentyl; (C1-C5 haloalkyl)carbonyl C1-C5 alkyl may include 3,3,3-trifluoro-2-oxopropyl; hydroxy C1-C5 alkyl may include 2-hydroxyethyl and 4-hydroxybutyl; C1-C5 alkoxy C1-C5 alkyl may include methoxymethyl, 1-methoxyethyl, and ethoxymethyl; C1-C5 alkylthio C1-C5 alkyl may include methylthiomethyl and methylthioethyl; (C1-C5 alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, and t-butoxycarbonyl; carboxy C1-C5 alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C1-C10alkoxy)carbonyl C1-C5 alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonyl; (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl may include 4-fluorocyclohexyloxycarbonylmethyl; (C3-C10alkenoxy)carbonyl C1-C5 alkyl may include allyoxycarbonylmethyl, 1-methyl-2-propenyloxycarbonylmethyl, 1-allyloxycarbonylethyl, and 1-(1-methyl-2-propenyloxy)carbonylethyl; (C1-C10 alkynoxy)carbonyl C1-C5 alkyl may include propargyloxycarbonylmethyl, 1-methyl-2-propynyloxycarbonylmethyl, 1-propargyloxycarbonylethyl, 1-(1-methyl-2-propynyloxy)carbonylethyl; carboxy(C1-C5 alkoxy)carbonyl C1-C5 alkyl may include carboxymethoxycarbonylmethyl, 1-carboxyethoxycarbonylmethyl, 1-carboxy-1-methylethoxycarbonylmethyl, 1-(carboxymethoxycarbonyl)ethyl, 1-(1-carboxyethoxycarbonyl)ethyl, and 1-(1-carboxy-1-methylethoxycarbonyl)ethyl; (C1-C10alkoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl may include methoxycarbonylmethoxycarbonylmethyl, 1-methoxycarbonylethoxycarbonylmethyl, 1-methoxycarbonyl-1-methylethoxycarbonylmethyl, 1-(methoxycarbonylmethoxycarbonyl)ethyl, 1-(1-meth oxycarbonylethoxycarbonyl)ethyl, 1-(1-methoxycarbonyl-1-methylethoxycarbonyl)ethyl, ethoxycarbonylmethoxycarbonylmethyl, 1-ethoxycarbonylethoxycarbonylmethyl, 1-ethoxycarbonyl-1-methylethoxycarbonylmethyl, 1-(ethoxycarbonylmethoxycarbonyl)ethyl, 1-(1-ethoxycarbonylethoxycarbonyl)ethyl, 1-(1-ethoxycarbonyl-1-methylethoxycarbonyl)ethyl, isopropoxycarbonylmethoxycarbonylmethyl, 1-isopropoxycarbonylethoxycarbonylmethyl, 1-isopropoxycarbonyl-1-methylethoxycarbonylmethyl, 1-(isopropoxycarbonylmethoxycarbonyl)ethyl, 1-(1-isopropoxycarbonylethoxycarbonyl)ethyl, and 1-(1-isopropoxycarbonyl-1-methylethoxycarbonyl)ethyl; (C1-C10 haloalkoxy)carbonyl-(C1-C5 alkoxy)carbonyl C1-C5 alkyl may include 2-chloroethoxycarbonylmethoxycarbonylmethyl, 1-(2-chloroethoxycarbonyl)ethoxycarbonylmethyl, 1-(2-chloroethoxycarbonyl)-1-methylethoxycarbonylmethyl, 1-(2-chloroethoxycarbonylmethoxycarbonyl)ethyl, 1-{1-(2-chloroethoxycarbonyl)ethoxycarbonyl}ethyl, and 1-{1-(2-chloroethoxycarbonyl)-1-methylethoxycarbonyl}ethyl; (C3-C10 cycloalkoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl may include cyclopentyloxycarbonylmethoxycarbonylmethyl, 1-cyclopentyloxycarbonylethoxycarbonylmethyl, 1-cyclopentyloxycarbonyl-1-methylethoxycarbonylmethyl, 1-(cyclopentyloxycarbonylmethoxycarbonyl)ethyl, 1-(1-cyclopentyloxycarbonylethoxycarbonyl)ethyl, 1-(1-cyclopentyloxycarbonyl-1-methylethoxycarbonyl)ethyl, cyclohexyloxycarbonylmethoxycarbonylmethyl, 1-cyclohexyloxycarbonylethoxycarbonylmethyl, 1-cyclohexyloxycarbonyl-1-methylethoxycarbonylmethyl, 1-(cyclohexyloxycarbonylmethoxycarbonyl)ethyl, 1-(1-cyclohexyloxycarbonylethoxycarbonyl)ethyl, and 1-(1-cyclohexyloxycarbonyl-1-methylethoxycarbonyl)ethyl; (C3-C10 alkenoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl may include allyloxycarbonylmethoxycarbonylmethyl, 1-allyloxycarbonylethoxycarbonylmethyl, 1-allyloxycarbonyl-1-methylethoxycarbonylmethyl, 1-(allyloxycarbonylmethoxycarbonyl)ethyl, 1-(1-allyloxycarbonylethoxycarbonyl)ethyl, and 1-(1-allyloxycarbonyl-1-methylethoxycarbonyl)ethyl; (C3-C10 alkynoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl may include propargyloxycarbonylmethoxycarbonylmethyl, 1-propargyloxycarbonylethoxycarbonylmethyl, 1-propargyloxycarbonyl-1-methylethoxycarbonylmethyl, 1-(propargyloxycarbonylmethoxycarbonyl)ethyl, 1-(1-propargyloxycarbonylethoxycarbonyl) ethyl, and 1-(1-propargyloxycarbonyl-1-methylethoxycarbonyl)ethyl; carboxy(C1-C5 alkyl)carbonyl may include carboxymethylcarbonyl, carboxyethylcarbonyl, 1-carboxy-1-methylethylcarbonyl, 2-carboxyethylcarbonyl, 3-carboxypropylcarbonyl, and 3-carboxy-1-methylpropylcarbonyl; (C1-C10 alkoxy)carbonyl(C1-C5 alkyl)carbonyl may include methoxycarbonylmethylcarbonyl, 1-methoxycarbonylethylcarbonyl, 1-methoxycarbonyl-1-methylethylcarbonyl, 2-methoxycarbonylethylcarbonyl, 3-methoxycarbonylpropylcarbonyl, 3-methoxycarbonyl-1-methylpropylcarbonyl, ethoxycarbonylmethylcarbonyl, 1-ethoxycarbonylethylcarbonyl, 1-ethoxycarbonyl-1-methylethylcarbonyl, 2-ethoxycarbonylethylcarbonyl, 3-ethoxycarbonylpropylcarbonyl, and 3-ethoxycarbonyl-1-methylpropylcarbonyl; (C1-C10haloalkoxy)carbonyl(C1-C5 alkyl)carbonyl may include 2-chloroethoxycarbonylmethylcarbonyl, 2,2,2-trifluoroethoxycarbonylmethylcarbonyl, 3-bromopropoxycarbonylmethylcarbonyl, 1-(2-chloroethoxy)carbonylethylcarbonyl, and 1-(2,2,2-trifluoroethoxy)carbonylethylcarbonyl; C1-C5 alkylsulfonyl may include methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, and butylsulfonyl; C1-C5 haloalkylsulfonyl may include chloromethylsulfonyl, and trifluoromethylsulfonyl; optionally substituted benzyl may include benzyl; and optionally substituted phenyl may include phenyl.

[0084] For the groups represented by R13 or R63, C1-C10 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, and isoamyl; C1-C10 haloalkyl may include trifluoromethyl; carboxy C1-C5 alkyl may include carboxymethyl, carboxyethyl, 1-carboxyethyl, and 2-carboxypropyl; (C1-C10 alkoxy)carbonyl C1-C5 alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C3-C110 cycloalkoxy)carbonyl C1-C5 alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C3-C10halocycloalkoxy)carbonyl C1-C5 alkyl may include 4-fluorocyclo hexyloxycarbonylmethyl.

[0085] For the groups represented by R14 or R64, C1-C10 alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; C1-C10haloalkyl may include 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifluoroethyl; C3-C10cycloalkyl may include cyclopentyl and cyclohexyl; C3-C10 halocycloalkyl may include 4,4,-difluorocyclopentyl and 3-chlorocyclohexyl; C3-C10cycloalkyl C1-C3 alkyl may include cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl; C3-C10alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C3-C10 haloalkenyl may include 2-chloro-2-propenyl, and 3,3-dichloro-2-propenyl; C3-C10 alkynyl may include propargyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, and 1,1-dimethyl-2-propynyl; C3-C10 haloalkynyl may include 3-iodo-2-propynyl, and 3-bromo-2-propynyl; carboxy C1-C5 alkyl may include carboxymethyl, 1-carboxyethyl, 2-carboxyethyl, and 1-carboxy-1-methylethyl; (C1-C10 alkoxy)carbonyl C1-C5 alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-methoxycarbonyl-1-methylethyl, 1-ethoxycarbonyl-1-methylethyl, 1-propoxycarbonyl-1-methylethyl, 1-isopropoxycarbonyl-1-methylethyl, 1-butoxycarbonyl-1-methylethyl, 1-isobutoxycarbonyl-1-methylethyl, 1-t-butoxycarbonyl-1-methylethyl, 1-amyloxycarbonyl-1-methylethyl, 1-isoamyloxycarbonyl-1-methylethyl, and 1-t-butoxycarbonyl-1-methylethyl; (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, 1-(2,2,2-trifluoroethoxy)carbonylethyl, 1-(2-chloroethoxy)carbonyl-1-methylethyl, and 1-(2,2,2-trifluoroethoxy)carbonyl-1-methylethyl; (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, 1-cyclohexyloxycarbonylethyl, 1-cyclopentyloxycarbonyl-1-methylethyl, and 1-cyclohexyloxycarbonyl-1-methylethyl; (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl may include 4-fluorocyclohexyloxycarbonylmethyl, and 1-(4-fluorocyclohexyloxycarbonyl)-1-methylethyl; (C3-C10 alkenoxy)carbonyl C1-C5 alkyl may include allyloxycarbonylmethyl, 1-methyl-2-propenyloxycarbonylmethyl, 1-allyloxycarbonylethyl, 1-(1-methyl-2-propenyloxy)carbonylethyl, 1-allyloxycarbonyl-1-methylethyl, and 1-(1-methyl-2-propenyloxy)carbonyl-1-methylethyl; (C1-C10 alkynoxy)carbonyl C1-C5 alkyl may include propargyloxycarbonylmethyl, 1-methyl-2-propynyloxycarbonylmethyl, 1-propargyloxycarbonylethyl, 1-(1-methyl-2-propynyloxy)carbonylethyl, 1-propargyloxycarbonyl-1-methylethyl, and 1-(1-methyl-2-propynyloxy)carbonyl-1-methylethyl; optionally substituted benzyl may include benzyl; and optionally substituted phenyl may include phenyl.

[0086] For the groups represented by R15 or R65, C1-C10 alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; C1-C10 haloalkyl may include 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifluoroethyl; C3-C10cycloalkyl may include cyclopentyl, and cyclohexyl; C3-C10cycloalkyl C1-C3 alkyl may include cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl; C3-C10 alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C3-C10 alkynyl may include propargyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, and 1,1-dimethyl-2-propynyl; cyano C1-C6 alkyl may include cyanomethyl, and cyanoethyl; carboxy C1-C5 alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C1-C10 alkoxy)carbonyl C1-C5 alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; optionally substituted benzyl may include benzyl; and optionally substituted phenyl may include phenyl.

[0087] For the groups represented by R16 or R16, C1-C10 alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; and C1-C10 haloalkyl may include 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifluoroethyl.

[0088] The 3- to 7-membered saturated ring, which is formed by combining R15 and R16 or R65 and R66 at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.

[0089] For the groups represented by R17, R26, R27, R67, R76, or R77, C1-C10 alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; C1-C10 haloalkyl may include 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifluoroethyl; C3-C10cycloalkyl may include cyclopentyl, and cyclohexyl; C3-C10cycloalkyl C1-C3 alkyl may include cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl; (C1-C6 alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, and isopropoxycarbonyl; and (C1-C6 alkoxy)carbonylmethyl may include methoxy carbonylmethyl, ethoxycarbonylmethyl, and isopropoxycarbonylmethyl.

[0090] For the groups represented by R19 or R69, C1-C10 alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; C1-C10haloalkyl may include 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifluoroethyl; C3-C10cycloalkyl may include cyclopentyl and cyclohexyl; C3-C10 halocycloalkyl may include 4,4,-difluorocyclopentyl and 3-chlorocyclohexyl; C3-C1 cycloalkyl C1-C3 alkyl may include cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl; C3-C10alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C3-C10 haloalkenyl may include 2-chloro-2-propenyl, and 3,3-dichloro-2-propenyl; C3-CC1, alkynyl may include propargyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, and 1,1-dimethyl-2-propynyl; C3-C10 haloalkynyl may include 3-iodo-2-propynyl, and 3-bromo-2-propynyl; cyano C1-C6 alkyl may include cyanomethyl and cyanoethyl; carboxy C1-C5 alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C1-C10alkoxy)carbonyl C1-C5 alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1- ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C1-C10haloalkoxy)carbonyl C1-C5 alkyl may include 2-chloroethoxycarbonylmethyl, 2,2, 2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.

[0091] For the elements or groups represented by R21 or R71, halogen may include fluorine, chlorine, bromine, and iodine; C1-C3 alkyl may include methyl and ethyl; and C1-C3 haloalkyl may include trifluoromethyl.

[0092] For the groups represented by R22, R25, R72, or R75, (C1-C10 alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, t-butoxycarbonyl, amyloxycarbonyl, and isoamyloxycarbonyl; (C1-C10 haloalkoxy)carbonyl may include 2-chloroethoxycarbonyl, 2-fluoroethoxycarbonyl,-3-bromopropoxycarbonyl, 3-chlorobutoxycarbonyl, and 5,5-dichloroamyloxycarbonyl; (C3-C10cycloalkoxy)carbonyl may include cyclopentyloxycarbonyl and cyclohexylcarbonyl; (C3-C10halocycloalkoxy)carbonyl may include 4,4-difluorocyclohexyloxycarbonyl; carboxy(C1-C5 alkoxy)carbonyl may include carboxymethoxycarbonyl, 1-carboxyethoxycarbonyl, and 1-carboxy-1-methylethoxycarbonyl; (C1-C10alkoxy)carbonyl(C1-C5 alkoxy)carbonyl may include methoxycarbonylmethoxycarbonyl, 1-methoxycarbonylethoxycarbonyl, 1-methoxycarbonyl-1-methylethoxycarbonyl, ethoxycarbonylmethoxycarbonyl, 1-ethoxycarbonylethoxycarbonyl, 1-ethoxycarbonyl-1-methylethoxycarbonyl, isopropoxycarbonylmethoxycarbonyl, 1-isopropoxycarbonylethoxycarbonyl, and 1-isopropoxycarbonyl-1-methylethoxycarbonyl; (C1-C10 haloalkoxy)carbonyl(C1-C5 alkoxy)carbonyl may include 2-chloroethoxycarbonylmethoxycarbonyl, 1-(2-chloroethoxycarbonyl)ethoxycarbonyl, and 1-(2-chloroethoxycarbonyl)-1-methylethoxycarbonyl; (C3- C10 cycloalkoxy)carbonyl(C1-C5 alkoxy)carbonyl may include cyclopentyloxycarbonylmethoxycarbonyl, 1-cyclopentyloxycarbonylethoxycarbonyl, 1-cyclopentyloxycarbonyl-1-methylethoxycarbonyl, cyclohexyloxycarbonylmethoxycarbonyl, 1-cyclohexyloxycarbonylethoxycarbonyl, and 1-cyclohexyloxycarbonyl-1-methylethoxycarbonyl; (C3-C10 alkenoxy)carbonyl(C1-C5 alkoxy)carbonyl may include allyloxycarbonylmethoxycarbonyl, 1-allyloxycarbonylethoxycarbonyl, and 1-allyloxycarbonyl-1-methylethoxycarbonyl; and (C3-C10 alkynoxy)carbonyl(C1-C5 alkoxy)carbonyl may include propargyloxycarbonylmethoxycarbonyl, 1-propargyloxycarbonylethoxycarbonyl, and 1-propargyloxycarbonyl-1-methylethoxy carbonyl.

[0093] For the elements or groups represented by R23, R24, R73, or R74, halogen may include fluorine, chlorine, bromine, and iodine; C1-C3 alkyl may include methyl, and ethyl; and C1-C3 haloalkyl may include trifluoromethyl.

[0094] For the elements or groups represented by R43, R44, R13, or R164, halogen may include fluorine, chlorine, bromine, and iodine; C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; and C1-C5 haloalkyl may include trifluoromethyl.

[0095] For the groups represented by R45, R46, R165, or R166, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C3-C8 cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C3-C6 alkenyl may include allyl and 1-methylpropenyl; and C3-C6 alkynyl may include propargyl and 1-methylpropynyl.

[0096] The 3- to 7-membered saturated ring, which is formed by combining R45 and R46 or R165 and R166 at their ends, together with the adjacent nitrogen atom, may include aziridine ring, azetidine ring, pyrrolidine ring, and piperidine ring.

[0097] For the elements and groups represented by R47, R48, R167, or R168, halogen may include fluorine, chlorine, bromine, and iodine; C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; and C1-C5 haloalkyl may include trifluoromethyl.

[0098] For the groups represented by R49, R50, R169, or R170, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C3-C8 cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C3-C6 alkenyl may include allyl, and 1-methylpropenyl; and C3-C6 alkynyl may include propargyl and 1-methylpropynyl.

[0099] The 3- to 7-membered ring, which is formed by combining R49 and R50 or R169 and R170 at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.

[0100] For the groups represented by R51, R52, R171, or R172, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C3-C8 cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C3-C6 alkenyl may include allyl and 1-methylpropenyl; and C3-C6 alkynyl may include propargyl and 1-methylpropynyl.

[0101] The 3- to 7-membered ring, which is formed by combining R51 and R52 or R171 and R172 at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.

[0102] For the groups represented by R53, R54, R1, or R174, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C3-C8 cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C3-C6 alkenyl may include allyl and 1-methylpropenyl; and C3-C6 alkynyl may include propargyl and 1-methylpropynyl.

[0103] The 3- to 7-membered ring, which is formed by combining R53 and R54 or R173 and R174 at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.

[0104] For the groups represented by R55, R57, R75, or R177, C1-C3 alkyl may include methyl, ethyl, and propyl.

[0105] For the groups represented by R55, R57, R175, or R177, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; (C1-C5 alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, and propyloxycarbonyl; (C1-C5 haloalkoxy)carbonyl may include trifluoromethoxycarbonyl and 2,2,2-trifluoroethoxycarbonyl; (C3-C5 cycloalkoxy)carbonyl may include cyclopropyloxycarbonyl; (C3-C5 alkenoxy)carbonyl may include allyloxycarbonyl; and (C3-C5 alkynoxy)carbonyl may include propargyloxy carbonyl.

[0106] For the groups represented by R79 or R179, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2 ,2-trichloroethyl, and 3-bromopropyl; C3-C8 cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C3-C6 alkenyl may include allyl and 1-methylpropenyl; C1-C6 alkynyl may include propargyl and 1-methylpropynyl; carboxy C1-C5 alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C1-C10 alkoxy)carbonyl C1-C5 alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C1-C10 halocycloalkoxy) carbonyl C1-C5 alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.

[0107] For the groups represented by R80 or R180, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C3-C8 cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C3-C6 alkenyl may include allyl and 1-methyl propenyl; and C3-C6 alkynyl may include propargyl and 1-methylpropynyl.

[0108] The 3- to 7-membered ring, which is formed by combining R79 and R80 or R179 and R180 at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.

[0109] For the groups represented by R81 or R181, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C3-C8 cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C3-C6 alkenyl may include allyl and 1-methylpropenyl; C3-C6 alkynyl may include propargyl and 1-methylpropynyl; carboxy C1-C5 alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C1-C10 alkoxy)carbonyl C1-C5 alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C3-C10cycloalkoxy)carbonyl C1-C5 alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C3-C10halocycloalkoxy)carbonyl C1-C5 alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.

[0110] For the groups represented by R82 or R182, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C3-C8 cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C3-C6 alkenyl may include allyl and 1-methylpropenyl; C3-C6 alkynyl may include propargyl and 1-methylpropynyl; carboxy C1-C5 alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C1-C10 alkoxy)carbonyl C1-C5 alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamylpxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C1-C10haloalkoxy)carbonyl C1-C5 alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C3-C10halocydoalkoxy)carbonyl C1-C5 alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.

[0111] For the groups represented by R83 or R183, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C1-C8 cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C1-C6 alkenyl may include allyl and 1-methylpropenyl; and C3-C6 alkynyl may include propargyl and 1-methylpropynyl.

[0112] The 3- to 7-membered ring, which is formed by combining R82 and R83 or R182 and R183 at their ends, together with the adjacent nitrogen, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.

[0113] For the groups represented by R84 or R184, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C3-C8 cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C3-C6 alkenyl may include allyl and 1-methylpropenyl; C3-C6 alkynyl may include propargyl and 1-methylpropynyl; carboxy C1-C5 alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C1-C10alkoxy)carbonyl C1-C5 alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C3-C10halocycloalkoxy)carbonyl C1-C5 alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.

[0114] For the groups represented by R85 or R185, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C3-C8 cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C3-C6 alkenyl may include allyl and 1-methylpropenyl; and C3-C6 alkynyl may include propargyl and 1-methylpropynyl.

[0115] The 3- to 7-membered ring, which is formed by combining R84 and R85 or R84 and R185 at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.

[0116] For the groups represented by R16 or R186, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C3-C8 cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C3-C6 alkenyl may include allyl and 1-methylpropenyl; C3-C6 alkynyl may include propargyl and 1-methylpropynyl; carboxy C1-C5 alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C1-C10 alkoxy)carbonyl C1-C5 alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C3-C10 cycloalkoxy)carbonyl C3-C5 alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.

[0117] For the groups represented by R87 or R187, C1-C5 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C1-C5 haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C3-C8 cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C3-C6 alkenyl may include allyl and 1-methylpropenyl; and C3-C6 alkynyl may include propargyl and 1-methylpropynyl.

[0118] The 3- to 7-membered ring, which is formed by combining R86 and R87 or R186 and R187 at their ends, together with the adjacent nitrogen atom, may include aziridine ring, azetidine ring, pyrrolidine ring, and piperidine ring.

[0119] For the groups represented by E1 or E2, C1-C6 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, and chlorodifluoromethyl; and C1-C6 cycloalkyl optionally substituted with halogen may include cyclopropyl, cyclobutyl, and cyclopentyl.

[0120] The 4- to 7-membered unsaturated ring, which is formed by combining E1 and E2 at their ends and which contains, together with the atoms attached thereto on Q1, zero to two O, S, SO, SO2 or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E1 and E2.

[0121] For the groups represented by E3 or E4, C1-C6 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and 3-fluoropropyl; and C3-C6 cycloalkyl optionally substituted with halogen may include cyclopropyl, cyclobutyl, and cyclopentyl.

[0122] The 4- or 7-membered saturated or unsaturated ring, which is formed by combining E3 and E4 at their ends and which contains, together with the atoms attached thereto on Q2, zero to two O, S, SO, SO2 or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E3 and E4.

[0123] For the groups represented by E5, C1-C6 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, 2-fluoroethyl, 3-fluoropropyl, and 4-fluorobutyl.

[0124] For the groups or elements represented by E6 or E7, C1-C6 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and 3-fluoropropyl; and C3-C6 cycloalkyl optionally substituted with halogen may include cyclopropyl, cyclobutyl, and cyclopentyl.

[0125] The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E6 and E7 at their ends and which contains, together with the atoms attached thereto on Q4, zero to two O, S, SO, SO2 or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E6 and E7.

[0126] For the groups represented by E8 or E9, C1-C8 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and 3-fluoropropyl; and C3-C6 cycloalkyl optionally substituted with halogen may include cyclopropyl, cyclobutyl, and cyclopentyl.

[0127] The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E8 and E9 at their ends and which contains, together with the atoms attached thereto on Q5, zero to two O, S, SO, SO2 or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E8 and E9.

[0128] For the groups represented by E10, C1-C6 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and 3-fluoropropyl; and C1-C3 alkoxy optionally substituted with halogen may include methoxy, ethoxy, propoxy, isopropoxy, trifluoromethoxy, and difluoromethoxy.

[0129] For the groups represented by E11, C1-C6 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, pentafluoroethyl, and 3-fluoropropyl.

[0130] The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E10 and E11 at their ends and which contains, together with the atoms attached thereto on Q6, zero to two O, S, SO, SO2 or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E10 and E11.

[0131] For the elements or groups represented by E44, halogen may include fluorine, chlorine, bromine, or iodine; and C1-C3 alkyl may include methyl, ethyl, propyl, and isopropyl.

[0132] For the groups represented by E12, C1-C6 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

[0133] For the groups represented by E13, C1-C6 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

[0134] For the elements represented by E14, halogen may include chlorine, bromine, and iodine.

[0135] For the groups represented by E15, C1-C6 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, and amyl.

[0136] For the groups represented by E16, C1-C6 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

[0137] The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E15 and E16 at their ends and which contains, together with the atoms attached thereto on Q9, zero to two O, S, SO, SO2 or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E15 and E6.

[0138] For the groups represented by E17, E18, or E19, C1-C6 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl.

[0139] For the groups represented by E20 or E21, C1-C6 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl.

[0140] For the groups represented by E22 or E23, C1-C6 alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl.

[0141] For the groups represented by E24, C1-C3 alkyl may include methyl, ethyl, propyl, and isopropyl.

[0142] For the groups or elements represented by E25, C1-C3 alkyl may include methyl, ethyl, propyl, and isopropyl; and halogen may include fluorine, chlorine, bromine, and iodine.

[0143] For the groups represented by E26, C1-C3 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chloro difluoromethyl, and pentafluoroethyl.

[0144] For the groups represented by E27, C1-C6 alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, isoamyl, pentyl, and hexyl; C3-C6 alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C3-C6 alkynyl may include propargyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, and 1,1-dimethyl-2-propynyl; and optionally substituted benzyl may include benzyl.

[0145] For the groups represented by E28, C1-C3 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

[0146] For the groups represented by E29, C1-C6 alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, isoamyl, pentyl, and hexyl; C3-C6 alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C3-C6 alkynyl may include propargyl, 1-methyl-3-propynyl, 2-butynyl, 3-butynl, and 1,1-dimethyl-2-propynyl; and optionally substituted benzyl may include benzyl.

[0147] For the groups represented by E30 or E31, C1-C3 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

[0148] The 4- to 7-membered unsaturated ring, which is formed by combining E30 and E31 at their ends and which contains zero to two O, S, SO, SO2 or NH groups (which ring may optionally be substituted with methyl or halogen), may include the cases where tetramethylene or trimethylene is formed by E30 and E31.

[0149] For the groups represented by E42, C1-C3 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

[0150] For the groups represented by E32, C1-C3 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

[0151] For the elements or groups represented by E33, halogen may include chlorine, bromine, and iodine; C1-C3 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl and pentafluoroethyl; C1-C3 alkoxy optionally substituted with halogen may include methoxy and ethoxy; and C1-C3 alkylthio optionally substituted with halogen may include methylthio and ethylthio.

[0152] For the groups represented by E43, C1-C3 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoro ethyl.

[0153] For the groups represented by E34, C1-C3 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

[0154] For the groups represented by E35, C1-C3 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

[0155] For the groups represented by E36 or E37, C1-C6 alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, isoamyl, pentyl, and hexyl.

[0156] The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E36 and E37 at their ends and which contains, together with the atoms attached thereto on Q21, zero to two O, S, SO, SO2 or NH groups (which ring may optionally be substituted with methyl or halogen), may include the cases where tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E36 and E37.

[0157] For the groups represented by E38, C1-C6 alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, isoamyl, pentyl, and hexyl.

[0158] For the groups represented by E39, C1-C3 alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

[0159] The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E38 and E39 at their ends and which contains, together with the atoms attached thereto on Q22, zero to two O, S, SO, SO2 or NH groups (which ring may optionally be substituted with methyl or halogen), may include the cases where tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E38 and E39.

[0160] For the groups represented by E40, C1-C6 alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, isoamyl, pentyl, and hexyl.

[0161] For the groups represented by E41, C1-C3 alkyl may include methyl, ethyl, propyl, and isopropyl; and C3-C6 cycloalkyl may include cyclopropyl, cyclopentyl, and cyclohexyl.

[0162] The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E40 and E41 at their ends and which contains, together with the atoms attached thereto on Q23 (which ring may optionally be substituted with methyl or halogen), may include the cases where tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E40 and E41.

[0163] For the present compounds, there may exist geometrical isomers based on the presence of a double bond, or optical isomers and diastereomers based on the presence of at least one asymmetric carbon atom, and all of these isomers and their mixtures are also included within the scope of the present invention.

[0164] The preferred substituents from the viewpoint of herbicidal activity may include CH, CCH3, CCl, CBr and N, more preferably CH and N, for A, and Q1, Q2, Q4, Q6, Q14, Q16, Q18, Q19 and Q20 for Q.

[0165] When Q is Q1, compounds in which E1 and E2 are combined at their ends to form, together with the atoms attached thereto, a 5- to 7-membered unsaturated ring are preferred, and in particular, compounds in which the unsaturated ring is a 6-membered ring are more preferred.

[0166] When Q is Q2, compounds in which E3 and E4 are combined at their ends to form, together with the atoms attached thereto, a 5- to 7-membered saturated or unsaturated ring are preferred, and in particular, compounds in which the saturated or unsaturated ring is a 6-membered ring and D1 and D2 are oxygen are more preferred.

[0167] When Q is Q4, compounds in which E6 is C1-C6 alkyl optionally substituted with halogen and E7 is C1-C6 alkyl optionally substituted with halogen are preferred, and in particular, compounds in which E6 is methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl) or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl) and E7 is methyl or ethyl are more preferred. In addition, compounds in which E6 and E7 are combined at their ends to form, together with the atoms attached thereto, a 5- or 7-membered saturated or unsaturated ring are preferred, and in particular, compounds in which the saturated or unsaturated ring is a 6-membered ring are more preferred.

[0168] When Q is Q6, compounds in which E10 is C1-C6 alkyl optionally substituted with halogen, E11 is C1-C6 alkyl optionally substituted with halogen, and E44 is chlorine or bromine are preferred, and in particular, compounds in which E10 is methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl) or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl) and E11 is methyl or ethyl are more preferred. In addition, compounds in which E10 and E11 are combined at their ends to form, together with the atoms attached thereto, a 5- to 7-membered saturated or unsaturated ring are preferred, and in particular, compounds in which the saturated or unsaturated ring is a 6-membered ring are more preferred.

[0169] When Q is Q14, compounds in which D7 is oxygen, E25 is hydrogen, E26 is C1-C, alkyl optionally with halogen, and E27 is C1-C3 alkyl are preferred, and in particular, compounds in which E26 is methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl) or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1, 1-difLuoroethyl) and E27 is methyl or ethyl are more preferred.

[0170] When Q is Q16, compounds in which E30 is C1-C3 alkyl optionally substituted with halogen, E31 is hydrogen or C1-C3 alkyl, and E42 is hydrogen or C1-C3 alkyl are preferred, and in particular, compounds in which E30 is methyl, methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl), or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl), E31 is hydrogen or methyl, and E42 is hydrogen or methyl are more preferred. In addition, compounds in which E30 and E31 are combined at their ends to form, together with the atoms attached thereto, a 5- or 7-membered saturated or unsaturated ring are preferred, and in particular, compounds in which the saturated or unsaturated ring is a 5- or 6-membered ring are more preferred.

[0171] When Q is Q18, compounds in which E34 is C1-C3 alkyl optionally substituted with halogen are preferred, and in particular, compounds in which E34 is methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl) or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl) are more preferred.

[0172] When Q is Q19, compounds in which V1 is —CH2— or —CH2—CH2— are preferred.

[0173] When Q is Q20, compounds in which E35 is C1-C3 alkyl optionally substituted with halogen, Z2 is nitrogen, and V2 is —CH2—CH2— or —CH═CH— are preferred, and in particular, compounds in which E11 is methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl) or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl) are more preferred.

[0174] Specific examples of the preferred compounds are recited below:

[0175] Methyl 3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;

[0176] Ethyl 3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydro pyrimidin-1-yl]benzo[b]furan-5-carboxylate;

[0177] Isopropyl 3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetra hydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;

[0178] Methyl 3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydro pyrimidin-1-yl]-6-nitrobenzo[b]furan-5-carboxylate;

[0179] Ethyl 3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydro pyrimidin-1-yl]-6-nitrobenzo[b]furan-5-carboxylate;

[0180] Methyl 6-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;

[0181] Ethyl 6-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;

[0182] Methyl 7-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;

[0183] Ethyl 7-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;

[0184] 3-(5-Methoxybenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

[0185] 3-(5-Methoxy-6-nitrobenzo[b]furan-3-yl)-1-methyl-6-(trifluoro methyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

[0186] 3-(6-Chloro-5-methoxyb enzo[b]furan-3-yl)-1-methyl-6-(trifluoro methyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

[0187] 3-(7-Chloro-5-methoxybenzo[b]furan-3-yl)-1-methyl-6-(trifluoro methyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

[0188] 3-[5-(Allyloxy)benzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

[0189] 3-[5-(Allyloxy)-6-nitrobenzo[b]furan-3-yl]-1-methyl-6-(trifluoro methyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

[0190] 3-[5-(Allyloxy)-6-chlorobenzo[b]furan-3-yl]-1-methyl-6-(trifluoro methyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

[0191] 3-[5-(Allyloxy)-7-chlorobenzo[b]furan-3-yl]-1-methyl-6-(trifluoro methyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

[0192] 1-Methyl-3-[5-(prop-2-ynyloxy)benzo[b]furan-3-yl]-6-(trifluoro methyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

[0193] 1-Methyl-3-[6-nitro-5-(prop-2-ynyloxy)b enzo[b]furan-3-yl]-6-(tri fluoromethyl)-1,2,3 ,4-tetrahydropyrimidine-2,4-dione;

[0194] 3-[6-Chloro-5-(prop-2-ynyloxy)benzo[b]furan-3-yl]-1-methyl-6-(tri fluoromethyl)-1,2,3,4-tetrahydiopyrimidine-2,4-dione;

[0195] 3-[7-Chloro-5-(prop-2-ynyloxy)benzo[b]furan-3-yl]-1-methyl-6-(tri fluoromethyl)-1,2,3 ,4-tetrahydropyrimidine-2,4-dione;

[0196] Ethyl 2-({3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetra hydropyr imidin-1-yl]benzo[b]furan-5-yl}oxy)propanoate;

[0197] Ethyl 2-({6-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-yl}oxy)propanoate;

[0198] Ethyl 2-({7-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-yl}oxy)propanoate;

[0199] 1-Methyl-3-[5-(methylthio)benzo[b]furan-3-yl]-6-(trifluoromethyl) -1,2,3,4-tetrahydropyrimidine-2,4-dione;

[0200] 1-Methyl-3-[5-(methylthio)-6-nitrobenzo[b]furan-3-yl]-6-(trifluoro methyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

[0201] 3-[6-Chloro-5-(methylthio)benzo[b]furan-3-yl]-1-methyl-6-(trifluoro methyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

[0202] 3-[7-Chloro-5-(methylthio)benzo[b]furan-3-yl]-1-methyl-6-(trifluoro methyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

[0203] Ethyl 2-({3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetra hydropyrimidin-1-yl]-6-nitrobenzo[b]furan-5-yl}thio)propanoate;

[0204] Ethyl 2-({6-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-yl}thio)propanoate;

[0205] Ethyl 2-({7-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-yl}thio)propanoate;

[0206] 3-(5,7-Dichlorobenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

[0207] 3-(5-Bromo-7-chlorobenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione; and

[0208] 3-(7-Chloro-5-methylbenzo[b]furan-3-yl)-1-methyl-6-(trifluoro methyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione.

[0209] The present compounds can be produced, for example, by Producing Processes 1 to 27 as described below.

[0210] Producing Process 1

[0211] In the process, compound a-1 of the general formula: 7

[0212] wherein T, A, Y, R1, R2, R3, and R4 are as defined above, is reacted with acid anhydride a-5 of the general formula: 8

[0213] wherein E1 and E2 are as defined above.

[0214] The reaction is carried out without solvent or in a solvent. The reaction temperature is usually in the range of 50° C. to 200° C. The reaction time is usually in the range of 1 to 100 hours. The amounts of reagents to be used in the reaction are 1 mole of acid anhydride a-5 relative to 1 mole of compound a-1, which is the stoichiometric ratio but can be freely changed depending upon the reaction conditions.

[0215] The solvent which can be used may include aliphatic hydrocarbons such as hexane, heptane, octane, and ligroin; aromatic hydrocarbons such as benzene, toluene, ethylbenzene, xylene, and mesitylene; halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, and trichlorobenzene; ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and methyl t-butyl ether; nitro compounds such as nitromethane and nitrobenzene; organic acids such as acetic acid and propionic acid; acid amides such as N,N-dimethylformamide; sulfur compounds such as dimethyl-sulfoxide and sulforane; and mixtures thereof. In addition, acids such as p-toluenesulfonic acid can also be used as a reaction catalyst.

[0216] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography. (see JP-A55-139359.)

[0217] Producing Process 2

[0218] This is the producing process according to the following scheme: 9

[0219] wherein R1, R2, R3, R4, D1, D2, E3, E4, T, A, and Y are as defined above, R200 is C1-C5 alkyl (e.g., methyl, ethyl) or hydrogen.

[0220] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 61-27985, or for example, by the following processes.

[0221] 1) Process of Producing Compound a-2 from Compound a-1

[0222] Compound a-2 can be produced by converting compound a-1 into an isocyanate or isothiocyanate derivative in a solvent or without solvent.

[0223] Agent for conversion into isocyanate or isothiocyanate derivatives: phosgene, trichloromethyl chloroformate, oxalyl chloride, thiophosgene, etc.

[0224] Amount of agent for conversion into isocyanate or isothiocyanate derivatives: 1 equivalent to an excess amount relative to 1 mole of compound a-1

[0225] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; etc.

[0226] Reaction temperature: room temperature to the reflux temperature of the agent for conversion into isocyanate or isothiocyanate derivatives Reaction time: a moment to 48 hours

[0227] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected -by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0228] 2) Process of Producing Compound a-3 from Compound a-2

[0229] Compound a-3 can be produced by reacting compound a-2 with compound a-6 of the general formula: 10

[0230] wherein D1, E3, E4, and R200 are as defined above, in a solvent in the presence of a base.

[0231] Amount of compound a-6: 1 to 5 moles relative to 1 mole of compound a-2

[0232] Kind of base: inorganic bases such as sodium hydride and potassium carbonate; organic bases such as triethylamine; metal alcoholates such as sodium methylate; etc.

[0233] Amount of base: 0.1 to 10 moles relative to 1 mole of compound a-2

[0234] Solvents: ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as ethanol; and mixtures thereof; etc.

[0235] Reaction temperature: −15° C. to the reflux temperature of the solvent

[0236] Reaction time: a moment to 96 hours

[0237] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0238] Compound a-4 may be directly obtained depending upon the reaction conditions of this process.

[0239] 3) Process of Producing Compound a-4 from Compound a-3

[0240] Compound a-4 can be produced by reacting compound a-3 in a solvent in the presence of a base.

[0241] Kind of base: inorganic bases such as sodium hydride; metal alcoholates such as sodium methylate; etc.

[0242] Amount of base: 1 to 5 moles relative to 1 mole of compound a-3

[0243] Solvent: ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as methanol and ethanol; and mixtures thereof, etc.

[0244] Reaction temperature: −10° C. to the reflux temperature of the solvent Reaction time: a moment to 96 hours

[0245] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0246] Producing Process 3

[0247] This is the producing process according to the following scheme: 11

[0248] wherein R1, R2, R3, R4, R200, D1, D2, E3, E4, T, A, and Y are as defined above.

[0249] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 61-27985, or for example, by the following processes.

[0250] 1) Process of Producing Compound b-3 from Compound a-2 Compound b-3 can be Produced by Reacting Compound a-2 With Compound b-5 of the General Formula: 12

[0251] wherein D1, E3, E4, and R200 are as defined above, in a solvent in the presence of a base.

[0252] Amount of compound b-5: 1 to 5 moles relative to 1 mole of compound a-2

[0253] Kind of base: inorganic bases such as sodium hydride and potassium carbonate; organic bases such as triethylamine; metal alcoholates such as sodium methylate; etc.

[0254] Amount of base: 0.1 to 10 moles relative to 1 mole of compound a-2 Solvent: ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as ethanol; and mixtures thereof; etc.

[0255] Reaction temperature: −15° C. to the reflux temperature of the solvent

[0256] Reaction time: a moment to 96 hours

[0257] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0258] Compound b-4 may be directly obtained depending upon the reaction conditions of this process.

[0259] 2) Process of Producing Compound b-4 from Compound b-3 Compound b-4 can be Produced by Reacting Compound b-3 in a Solvent in the Presence of a base.

[0260] Kind of base: inorganic bases such as sodium hydride; metal alcoholates such as sodium methylate; etc.

[0261] Amount of base: 1 to 5 moles relative to 1 mole of compound b-3

[0262] Solvent: ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as methanol and ethanol; and mixtures thereof; etc.

[0263] Reaction temperature: −10° C. to the reflux temperature of the solvent

[0264] Reaction time: a moment to 96 hours

[0265] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0266] Producing Process 4

[0267] This is the producing process according to the following scheme: 13

[0268] wherein R1, R2, R3, R4, D3, E5, T, A, and Y are as defined above.

[0269] The reactions in the respective steps can be carried out, for example, according to the processes as described in WO87/03873, or for example, by the following processes.

[0270] 1) Process of Producing Compound c-1 from Compound a-1

[0271] Compound c-1 can be produced from compound a-1 according to the process as described above in Producing Process 2, Step 1).

[0272] 2) Process of Producing Compound c-2 from Compound c-1

[0273] Compound c-2 can be produced by reacting compound c-1 and trimethylsilyl azide in a solvent or without solvent

[0274] Amount of trimethylsilyl azide: 1 to 3 moles relative to 1 mole of compound c-1

[0275] Solvent: benzene, toluene, chlorobenzene, etc.

[0276] Reaction temperature: room temperature to the reflux temperature

[0277] Reaction time: a moment to 48 hours

[0278] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0279] 3) Process of Producing Compound c-3 from Compound c-2

[0280] Compound c-3 can be produced by reacting compound c-2 and compound c-4 of the general formula:

M1-E5  c-4

[0281] wherein E5 is as defined above and M1 is chlorine, bromine, iodine, or methanesulfonyloxy, in a solvent in the presence of a base.

[0282] Amount of compound c-4: 1 to 3 moles relative to 1 mole of compound c-2

[0283] Kind of base: sodium hydride, potassium carbonate, etc.

[0284] Amount of base: 1 to 10 moles relative to 1 mole of compound c-2

[0285] Solvent: N,N-dimethylformamide, tetrahydrofuran, etc.

[0286] Reaction temperature: room temperature to 150° C.

[0287] Reaction time: a moment to 48 hours

[0288] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0289] Producing Process 5

[0290] This is the producing process according to the following scheme: 14

[0291] wherein R201 is methoxy, ethoxy or dimethylamino; and R1, R2, R3, R4, E6, E7, T, A, and Y are as defined above.

[0292] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 60-149571, or for example, by the following processes.

[0293] 1) Process of Producing Compound d-1 from Compound a-1

[0294] Compound d-1 can be produced by converting compound a-1 into a diazonium salt with sodium nitrite in the presence of an acid and then reacting the diazonium salt with a reducing agent such as tin (II) chloride. (see Organic Synthesis Collective Volume 1, p. 442.)

[0295] (Diazonium Salt Formation)

[0296] Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound a-1

[0297] Kind of acid: hydrochloric acid etc.

[0298] Amount of acid: 1 mole to an excess amount relative to 1 mole of compound a-1

[0299] Solvent: water, ethanol, hydrochloric acid, etc.

[0300] Reaction temperature: −15° C. to room temperature

[0301] Reaction time: a moment to 24 hours

[0302] (Reduction Reaction)

[0303] Kind of reducing agent: tin (II) chloride etc.

[0304] Amount of reducing agent: 3 to 10 moles relative to 1 mole of compound a-1

[0305] Solvent: hydrochloric acid etc.

[0306] Reaction temperature: −15° C. to room temperature

[0307] Reaction time: a moment to 48 hours

[0308] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0309] 2) Process of Producing Compound d-3 from Compound d-1

[0310] Compound d-3 can be produced by reacting compound d-1 and compound d-5 of the general formula: 15

[0311] wherein E7 and R201 are as defined above and R202 is methyl or ethyl, in a solvent, if necessary, in the presence of a base, to give intermediate d-2 and then reacting the intermediate d-2 in the presence of a base.

[0312] Intermediate d-2 may be isolated.

[0313] (Reaction of Compound d-1 into Compound d-2)

[0314] Amount of compound d-5: 1 to 3 moles relative to 1 mole of compound d-1.

[0315] Kind of base: organic bases such as triethylamine and pyridine; metal alcoholates such as sodium methylate and sodium ethylate; inorganic bases such as sodium hydroxide and potassium carbonate; etc.

[0316] Solvent: aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as ethanol and isopropanol; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; etc.

[0317] Reaction temperature: 0° C. to the reflux temperature of the solvent

[0318] Reaction time: a moment to 48 hours

[0319] (Reaction of Compound d-2 into Compound d-3)

[0320] Kind of base: organic bases such as triethylamine and pyridine; metal alcoholates such as sodium methylate and sodium ethylate; inorganic bases such as sodium hydroxide and potassium carbonate; etc.

[0321] Amount of base: 0.1 to 10 moles relative to 1 mole of compound a-1

[0322] Solvent: aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as ethanol and isopropanol; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; etc.

[0323] Reaction temperature: 0° C. to the reflux temperature of the solvent Reaction time: a moment to 48 hours After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0324] 3) Process of Producing Compound d-4 from Compound d-3

[0325] Compound d-4 can be produced by reacting compound d-3 with compound d-6 of the general formula:

M1-E6  d-6

[0326] wherein E6 and M1 are as defined above, in a solvent in the presence of a base.

[0327] Amount of compound d-6: 1 to 3 moles relative to 1 mole of compound d-3

[0328] Kind of base: sodium hydride, potassium carbonate, etc.

[0329] Amount of base: 1 to 10 moles relative to 1 mole of compound d-3

[0330] Solvent: N,N-dimethylformamide, tetrahydrofuran, etc.

[0331] Reaction temperature: 0° C. to the reflux temperature of the solvent

[0332] Reaction time: a moment to 48 hours

[0333] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0334] Compound d-3 can also be produced according to the following scheme. (see JP-A 7-503253.) 16

[0335] wherein R1, R2, R3, R4, E7, T, A, and Y are as defined above.

[0336] 1) Process of Producing Compound e-1 from Compound d-1

[0337] Compound e-1 can be produced by reacting compound d-1 with compound e-3 of the general formula: 17

[0338] wherein E7 is as defined above, in a solvent.

[0339] Amount of compound e-3: 1 to 10 moles relative to 1 mole of compound d-1

[0340] Solvent: water; alcohols such as ethanol and t-butanol; and mixtures thereof; etc.

[0341] Reaction temperature: −15° C. to 70° C.

[0342] Reaction time: a moment to 24 hours

[0343] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0344] Compound e-1 can also be used as such for the reaction in the next step without isolation.

[0345] 2) Process of Producing Compound e-2 from Compound e-1

[0346] Compound e-2 can be produced by reacting compound e-1 with an alkali metal cyanate, in a solvent, if necessary, in the presence of an acid.

[0347] Kind of alkali metal cyanate: NaOCN, KOCN, etc.

[0348] Amount of alkali metal cyanate: 1 to 3 moles relative to 1 mole of compound e-1

[0349] Kind of acid: organic acids such as acetic acid

[0350] Amount of acid: 0.01 to 1 mole relative to 1 mole of compound e-1

[0351] Solvent: water; alcohols such as ethanol and t-butanol; and mixtures thereof; etc.

[0352] Reaction temperature: −15° C. to 80° C.

[0353] Reaction time: a moment to 48 hours

[0354] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0355] Compound e-2 can also be used as such in the next step without isolation.

[0356] 3) Process of Producing Compound d-3 from Compound e-2

[0357] Compound d-3 can be produced by oxidizing compound e-2 with an oxidizing agent such as halogen, hypohalous acid, or hypohalite in a solvent.

[0358] Kind of oxidizing agent: chlorine, hypochlorous acid, sodium hypochlorite, etc.

[0359] Amount of oxidizing agent: 1 to 3 moles relative to 1 mole of compound e-2

[0360] Solvent: water; alcohols such as ethanol and t-butanol; and mixtures thereof; etc.

[0361] Reaction temperature: −15° C. to 60° C.

[0362] Reaction time: a moment to 48 hours

[0363] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0364] Producing Process 6

[0365] This is the producing process according to the following scheme: 18

[0366] wherein R1, R2 R3, R4, E10, E11, T, A, and Y are as defined above; E144 is halogen; and R203 is methyl or ethyl.

[0367] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 60-233061, or for example, by the following processes.

[0368] 1) Process of Producing Compound f-2 from Compound d-1

[0369] Compound f-2 can be produced by reacting compound d-1 with compound f-4 of the general formula: 19

[0370] wherein E10, E11, and R203 are as defined above, in a solvent, if necessary, in the presence of an acid.

[0371] Amount of compound f-4: 1 to 10 moles relative to 1 mole of compound d-1

[0372] Solvent: water; alcohols such as ethanol, isopropanol and butanol; aromatic hydrocarbons such as benzene and toluene; organic acids such as acetic acid and propionic acid; and mixtures thereof; etc.

[0373] Kind of acid: p-toluenesulfonic acid, hydrochloric acid, acetic acid, etc.

[0374] Amount of acid: 0.0001 mole to an excess amount relative to 1 mole of compound d-1

[0375] Reaction temperature: room temperature to the reflux temperature of the solvent

[0376] Reaction time: a moment to 96 hours

[0377] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0378] 2) Process of Producing Compound f-3 from Compound f-2

[0379] Compound f-3 can be produced by reacting compound f-2 with a halogenating agent in a solvent or without solvent under normal pressure or increased pressure.

[0380] Kind of halogenating agent: phosphorous oxychloride, phosphorous pentachloride, oxalyl chloride, phosgene, trichloromethyl chloroformate, etc.

[0381] Amount of halogenating agent: 1 mole to an excess amount relative to 1 mole of compound f-2

[0382] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; etc.

[0383] Reaction temperature: 50° C. to 250° C.

[0384] Reaction time: a moment to 96 hours

[0385] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0386] The compounds wherein E10 is CF2H can also be produced according to the following scheme: 20

[0387] wherein R1, R2, R3, R4, E11, E144, T, A, and Y are as defined above.

[0388] 1) Process of Producing Compound g-2 from Compound g-1

[0389] Compound g-2 can be produced by reacting compound g-1 with a Vilsmeier reagent (prepared from dimethylformamide and a halide such as phosphorous oxychloride, phosphorous pentachloride, oxalyl chloride, phosgene or trichloromethyl chloroformate; see Jikken Kagaku Koza, 4th Edition, 21, p. 110) in a solvent or without solvent.

[0390] Amount of Vilsmeier reagent: 1 to 20 moles relative to 1 mole of compound g-1

[0391] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

[0392] Reaction temperature: −10° C. to 150° C.

[0393] Reaction time: a moment to 96 hours

[0394] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0395] 2) Process of Producing Compound g-3 from Compound g-2

[0396] Compound g-3 can be produced by reacting compound g-2 with a fluorinating agent in a solvent.

[0397] Kind of fluorinating agent: dimethylaminosulfur trifluoride etc.

[0398] Amount of fluorinating agent: 1 to 10 moles relative to 1 mole of compound g-2

[0399] Solvent: halogenated aromatic hydrocarbons such as chlorobenzene; halogenated aliphatic hydrocarbons such as chloroform; etc.

[0400] Reaction temperature: −10° C. to room temperature

[0401] Reaction time: a moment to 96 hours

[0402] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and diied; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0403] Producing Process 7

[0404] This is the producing process according to the following scheme: 21

[0405] wherein R1, R2, R3, R4, E12, D4, T, A, and Y are as defined above.

[0406] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 60-109578, or for example, by the following processes.

[0407] 1) Process of Producing Compound h-1 from Compound d-1

[0408] Compound h-1 can be produced by reacting compound d-1 with an acylating agent selected from compound h-3 of the general formula: 22

[0409] wherein E1 2 is as defined above and R204 is hydrogen, methyl, or ethyl, compound h-4 of the general formula: 23

[0410] wherein E12 is as defined above, and compound h-5 of the general formula: 24

[0411] wherein E12 is as defined above, in a solvent or without solvent.

[0412] Amount of acylating agent: 1 to 5 moles relative to 1 mole of compound d-1

[0413] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

[0414] Reaction temperature: −10° C. to the reflux temperature of the solvent

[0415] Reaction time: a moment to 96 hours

[0416] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0417] 2) Process of Producing Compound h-2 from Compound h-1

[0418] Compound h-2 can be produced by reacting compound h-1 with compound h-6 of the general formula: 25

[0419] wherein D4 is as defined above, in a solvent in the presence of a base.

[0420] Amount of compound h-6: 1 to 5 moles of compound h-1

[0421] Kind of base: organic bases such as triethylamine and pyridine; inorganic bases such as potassium carbonate; etc.

[0422] Amount of base: 1 to 5 moles relative to 1 mole of compound h-1

[0423] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

[0424] Reaction temperature: −10° C. to room temperature

[0425] Reaction time: a moment to 96 hours

[0426] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0427] Producing Process 8

[0428] This is the producing process according to the following scheme: 26

[0429] wherein R1, R2, R3, R4, E13, T, A, and Y are as defined above; E114 is halogen; and R205 is methyl or ethyl.

[0430] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 6-145011, or for example, by the following processes.

[0431] 1) Process of Producing Compound i-1 from Compound a-1

[0432] Compound i-1 can be produced by reacting compound a-1 with a chloroformate i-5 of the general formula:

ClCOOR205  i-5

[0433] wherein R205 is as defined above, in a solvent in the presence of a base.

[0434] Amount of chloroformate i-5: 1 to 10 moles relative to 1 mole of compound a-1

[0435] Kind of base: N,N-dimethylaniline, N,N-diethylaniine, etc.

[0436] Amount of base: 1 to 10 moles relative to 1 mole of compound a-1

[0437] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

[0438] Reaction temperature: room temperature to the reflux temperature of the solvent

[0439] Reaction time: a moment to 96 hours

[0440] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0441] 2) Process of Producing Compound i-2 from Compound i-1

[0442] Compound i-2 can be produced by reacting compound i-1 with compound i-6 of the general formula: 27

[0443] wherein E13 is as defined above and M6 is chlorine or bromine, in a solvent in the presence of lithium bis(trimethylsilyl)amide.

[0444] Amount of compound i-6: 1 to 10 moles relative to 1 mole of compound i-1

[0445] Amount of lithium bis(tlimethylsilyl)amide: 1 to 10 moles relative to 1 mole of compound i-1

[0446] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

[0447] Reaction temperature: room temperature to the reflux temperature of the solvent

[0448] Reaction time: a moment to 96 hours

[0449] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0450] 3) Process of Producing Compound i-3 from Compound i-2

[0451] Compound i-3 can be produced by reacting compound i-2 with a halogenating agent in a solvent.

[0452] Kind of halogenating agent: chlorine, bromine, etc.

[0453] Amount of halogenating agent: 1 mole to large excess relative to 1 mole of compound i-2

[0454] Solvent: halogenated aromatic hydrocarbons such as chlorobenzene; halogenated aliphatic hydrocarbons such as chloroform; etc.

[0455] Reaction temperature: 10° C. to the reflux temperature of the solvent

[0456] Reaction time: a moment to 96 hours

[0457] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0458] 4) Process of Producing Compound i-4 from Compound i-3

[0459] Compound i-4 can be produced by reacting compound i-3 with a base in a solvent.

[0460] Kind of base: organic bases such as triethylamine and 1,8-diaza-bicylo[5.4.0]undec-7-ene; etc.

[0461] Amount of base: 1 mole to large excess relative to 1 mole of compound i-3

[0462] Solvent: dimethylsulfoxide etc.

[0463] Reaction temperature: 10° C. to the reflux temperature of the solvent

[0464] Reaction time: a moment to 96 hours

[0465] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0466] Producing Process 9

[0467] This is the producing process according to the following scheme: 28

[0468] wherein R1, R2, R3, R4, E15, E16, T, A, and Y are as defined above.

[0469] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 60-104073, or for example, by the following processes.

[0470] 1) Process of Producing Compound j-1 from Compound d-1

[0471] Compound j-1 can be produced by reacting compound d-1 with compound j-3 of the general formula: 29

[0472] wherein E15 and E16 are as defined above, in a solvent, if necessary, in the presence of an acid.

[0473] Amount of compound j-3: 1 to 5 moles relative to 1 mole of compound d-1

[0474] Solvent: toluene, ethanol, acetic acid, tetrahydrofuran, etc.

[0475] Acid: p-toluenesulfonic acid etc.

[0476] Reaction temperature: −10° C. to 100° C.

[0477] Reaction time: a moment to 48 hours

[0478] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried, or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0479] 2) Process of Producing Compound j-2 from Compound j-1

[0480] Compound j-2 can be produced by reacting compound j-1 with an oxidizing agent in a solvent in the presence of a pyridine.

[0481] Amount of pyridine: 1 to 2 moles relative to 1 mole of compound j-1

[0482] Kind of oxidizing agent: copper (II) sulfate etc.

[0483] Amount of oxidizing agent: 1 to 5 moles relative to 1 mole of compound j-1

[0484] Solvent: toluene, ethanol, acetic acid, tetrahydrofuran, etc.

[0485] Reaction temperature: −10° C. to 100° C.

[0486] Reaction time: a moment to 48 hours

[0487] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0488] Producing Process 10

[0489] This is the producing process according to the following scheme: 30

[0490] wherein R1, R2, R3, R4, E7, E18, E19, D5, T, A, and Y are as defined above and R206 is methyl or ethyl.

[0491] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 63-183567, or for example, by the following processes.

[0492] 1) Process of Producing Compound k-1 from Compound a-1

[0493] Compound k-1 can be produced from compound a-1 according to the process as described above in Producing Process 2, Step 1).

[0494] 2) Process of Producing Compound k-2 from Compound k-1

[0495] Compound k-2 can be produced by reacting compound k-1 with compound k-5 of the general formula: 31

[0496] wherein E18, E19, and R206 are as defined above, in a solvent in the presence of a base.

[0497] Amount of compound k-5: 1 to 2 moles relative to 1 mole of compound k-1

[0498] Kind of base: triethylamine, potassium carbonate, sodium hydride, sodium methylate, etc.

[0499] Amount of base: 1 to 5 moles relative to 1 mole of compound k-1 Solvent: toluene, ethanol, tetrahydrofuran, N,N-dimethylformamide, etc.

[0500] Reaction temperature: −10° C. to 100° C. Reaction time: a moment to 48 hours

[0501] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0502] Compound k-3 may be obtained directly depending upon the reaction conditions of this process.

[0503] 3) Process of Producing Compound k-3 from Compound k-2

[0504] Compound k-3 can be produced by reacting compound k-2 in a solvent in the presence of a base.

[0505] Kind of base: potassium carbonate, sodium hydride, sodium methylate, etc.

[0506] Amount of base: 1 to 5 moles relative to 1 mole of compound k-2

[0507] Solvent: toluene, ethanol, tetrahydrofuran, N,N-dimethylformamide, etc.

[0508] Reaction temperature: −10° C. to 100° C.

[0509] Reaction time: a moment to 48 hours

[0510] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0511] 4) Process of Producing Compound k-4 from Compound k-3

[0512] Compound k-4 can be produced by reacting compound k-3 with compound k-6 of the general formula:

M7-E17  k-6

[0513] wherein E17 is as defined above and M7 is iodine, bromine, or chlorine, in a solvent in the presence of a base.

[0514] Amount of compound k-6: 1 to 2 moles relative to 1 mole of compound k-3

[0515] Kind of base: triethylamine, potassium carbonate, sodium hydride, sodium methylate, etc.

[0516] Amount of base: 1 to 5 moles relative to 1 mole of compound k-3

[0517] Solvent: toluene, ethanol, tetrahydrofuran, N,N-dimethylformamide, etc.

[0518] Reaction temperature: −10° C. to 100° C. Reaction time: a moment to 48 hours

[0519] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0520] Producing Process 11

[0521] This is the producing process according to the following scheme: 32

[0522] wherein R1, R2, R3, R4, E20, E21, D6, T, A, and Y are as defined above and R207 is methyl or ethyl.

[0523] The reactions in the respective steps can be carried out, for example, according to the processes as described in WO87/62357, or for example, by the following processes.

[0524] 1) Process of Producing Compound 1-1 from Compound a-1

[0525] Compound 1-1 can be produced from compound a-1 according to the process as described above in Producing Process 2, Step 1).

[0526] 2) Process of Producing Compound 1-2 from Compound 1-1

[0527] Compound 1-2 can be produced by reacting compound 1-1 with compound 1-4 of the general formula: 33

[0528] wherein E20, E21, and R207 are as defined above, in a solvent in the presence of a base.

[0529] Amount of compound 1-4: 1 to 2 moles relative to 1 mole of compound 1-1

[0530] Kind of base: triethylamine, potassium carbonate, sodium hydride, sodium methylate, etc.

[0531] Amount of base: 1 to 5 moles relative to 1 mole of compound 1-1

[0532] Solvent: toluene, ethanol, tetrahydrofuran, N,N-dimethylformamide, etc.

[0533] Reaction temperature: −10° C. to 100° C.

[0534] Reaction time: a moment to 48 hours

[0535] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0536] Compound 1-3 may be obtained directly depending upon the reaction conditions of this process.

[0537] 3) Process of Producing Compound 1-3 from Compound 1-2

[0538] Compound 1-3 can be produced by reacting compound 1-2 in a solvent in the presence of a base.

[0539] Kind of base: potassium carbonate, sodium hydride, sodium methylate, etc.

[0540] Amount of base: 1 to 5 moles relative to 1 mole of compound 1-2

[0541] Solvent: toluene, ethanol, tetrahydrofuran, N,N-dimethylformamide, etc.

[0542] Reaction temperature: −10° C. to 100° C.

[0543] Reaction time: a moment to 48 hours

[0544] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0545] Producing Process 12

[0546] This is the producing process according to the following scheme: 34

[0547] wherein R1, R2, R3, R4, E22, E23, T, A, and Y are as defined above.

[0548] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 61-103801, or for example, by the following processes.

[0549] 1) Process of Producing Compound m-1 from Compound a-1

[0550] Compound m-1 can be produced by reacting compound a-1 with acid anhydride m-2 of the general formula: 35

[0551] wherein E22 and E23 are as defined above, usually without solvent, or in a solvent, if necessary, in the presence of an acid.

[0552] The reaction temperature is usually in the range of 50° C. to 200° C.

[0553] The reaction time is usually in the range of 1 to 100 hours. The amounts of agents to be used in the reaction are 1 mole of acid anhydride m-2 relative to 1 mole of compound a-1, which is the stoichiometric ratio but can be freely changed depending upon the reaction conditions.

[0554] The solvent which can be used may include aliphatic hydrocarbons such as hexane, heptane, octane, and ligroin; aromatic hydrocarbons such as benzene, toluene, ethylbenzene, xylene, and mesitylene; halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, and trichlorobenzene; ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and methyl t-butyl ether; nitro compounds such as nitromethane and nitrobenzene; organic acids such as acetic acid and propionic acid; acid amides such as N,N-dimethylformamide; sulfur compounds such as dimethylsulfoxide and sulforane; and mixtures thereof. As the acid, p-toluenesulfonic acid can be used.

[0555] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example,- the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0556] Producing Process 13

[0557] This is the producing process according to the following scheme: 36

[0558] wherein R1, R2, R3, R4, E24 T, A, and Y are as defined above.

[0559] The reactions in the respective steps can be carried out, for example, according to the processes as described in WO86/00072, or for example, by the following processes.

[0560] 1) Process of Producing Compound n-1 from Compound a-1

[0561] Compound n-1 can be produced by converting compound a-1 into a diazonium salt with sodium nitrite in a solvent in the presence of an acid and then reacting the diazonium salt with compound n-5 of the formula: 37

[0562] in a solvent in the presence of a base.

[0563] (Diazonium Salt Formation)

[0564] Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound a-1

[0565] Kind of acid: hydrochloric acid etc.

[0566] Amount of acid: 1 mole to an excess amount relative to 1 mole of compound a-1

[0567] Solvent: water, ethanol, hydrochloric acid, etc.

[0568] Reaction temperature: −15° C. to room temperature

[0569] Reaction time: a moment to 24 hours

[0570] (Reaction with Compound n-5)

[0571] Amount of compound n-5: 1 to 5 moles relative to 1 mole of compound a-1

[0572] Kind of base: sodium acetate etc.

[0573] Amount of base: 0.8 to 3 moles relative to 1 mole of acid used in the forgoing step

[0574] Solvent: ethanol, water, etc.

[0575] Reaction temperature: 0° C. to 60° C.

[0576] Reaction time: a moment to 48 hours

[0577] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0578] 2) Process of Producing Compound n-2 from Compound n-1

[0579] Compound n-2 can be produced by reacting compound n-1 in a solvent in the presence of a base.

[0580] Kind of base: sodium hydroxide, potassium hydroxide, etc.

[0581] Amount of base: 1 to 10 moles relative to 1 mole of compound n-1

[0582] Solvent: ethanol, N,N-dimethylformamide, water, and mixtures thereof; etc.

[0583] Reaction temperature: 0° C. to 110° C.

[0584] Reaction time: a moment to 48 hours

[0585] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0586] 3) Process of Producing Compound n-3 from Compound n-2

[0587] Compound n-3 can be Produced by reacting compound n-2 in a solvent in the presence of thioacetic acid.

[0588] Amount of thioacetic acid: 0.1 to 10 moles relative to 1 mole of compound n-2

[0589] Solvent: xylene etc.

[0590] Reaction temperature: reflux temperature

[0591] Reaction time: a moment to 72 hours

[0592] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0593] 4) Process of Producing Compound n-4 from Compound n-3

[0594] Compound n-4 can be produced by reacting compound n-3 with compound n-6 of the general formula:

M8-E24  n-6

[0595] wherein E24 is as defined above and M8 is iodine, bromine, or chlorine, in a solvent in the presence of a base.

[0596] Amount of compound n-6: 1 to 10 moles relative to 1 mole of compound n-3

[0597] Kind of base: potassium carbonate, sodium hydride, etc.

[0598] Amount of base: 1 to 10 moles relative to 1 mole of compound n-3

[0599] Solvent: acetone, tetrahydrofuran, N,N-dimethylformamide, etc.

[0600] Reaction temperature: 0° C. to 100° C.

[0601] Reaction time: a moment to 72 hours

[0602] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0603] Producing Process 14

[0604] This is the producing process according to the following scheme: 38

[0605] wherein R1, R2, R3, R4 E25, E26, E27, T, A, and Y are as defined above, and R208 and R209 are independently C1-C5 alkyl (e.g., methyl, ethyl, propyl).

[0606] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 5-4959 and JP-A 63-41466, or for example, by the following processes.

[0607] 1) Process of Producing Compound o-1 from Compound a-1

[0608] Compound o-1 can be produced from compound a-1 and chloroformate o-4 of the general formula:

ClCOOR208  o-4

[0609] wherein R208 is as defined above, according to the process as described above in Producing Process 8, Step 1).

[0610] 2) Process of Producing Compound o-11 from Compound o-1

[0611] Compound o-11 can be produced by reacting compound o-1 with compound o-5 of the general formula: 39

[0612] wherein E25, E26, and R209 are as defined above, in a solvent in the presence of a base.

[0613] Amount of compound o-5: 0.9 to 10 moles relative to 1 mole of compound o-1

[0614] Kind of base: inorganic bases such as sodium hydride; metal alcoholates such as sodium methylate and sodium ethylate; etc.

[0615] Amount of base: 0.1 to 10 moles relative to 1 mole of compound o-1

[0616] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; and mixtures thereof; etc.

[0617] Reaction temperature: room temperature to the reflux temperature of the solvent

[0618] Reaction time: a moment to 120 hours

[0619] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0620] Compound o-11 can also be used as such for the reaction in the next step without isolation.

[0621] 3) Process of Producing Compound o-2 from Compound o-11

[0622] Compound o-2 can be produced by reacting compound o-11 in a solvent in the presence of a base.

[0623] Kind of base: inorganic bases such as sodium hydride and potassium carbonate; metal alcoholates such as sodium methylate and sodium ethylate; etc.

[0624] Amount of base: 0.1 to 10 moles relative to 1 mole of compound o-11

[0625] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; sulfur compound such as dimethylsulfoxide; and mixtures thereof

[0626] Reaction temperature: room temperature to the reflux temperature of the solvent

[0627] Reaction time: a moment to 120 hours

[0628] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0629] Compound o-2 can also be used as such for the reaction in the next step without isolation.

[0630] 4) Process of Producing Compound o-3 from Compound o-2

[0631] Compound o-3 can be produced by reacting compound o-2 with compound o-6 of the general formula:

M9E27  o-6

[0632] wherein E27 is as defined above and M9 is iodine, bromine, chlorine, methanesulfonyloxy, or 2,4-dinitrophenoxy, in a solvent in the presence of a base.

[0633] Amount of compound o-6: 0.9 to 10 moles relative to 1 mole of compound o-2

[0634] Kind of base: inorganic bases such as sodium hydride, potassium carbonate, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

[0635] Amount of base: 0.1 to 10 moles relative to 1 mole of compound o-2

[0636] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

[0637] Reaction temperature: 0° C. to the reflux temperature of the solvent

[0638] Reaction time: a moment to 120 hours

[0639] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0640] Producing Process 15

[0641] This is the producing process according to the following scheme: 40

[0642] wherein R1, R2, R3, R4, D7, E25, E26, E27, T, A, andY are as defined above.

[0643] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 63-41466, or for example, by the following processes.

[0644] 1) Process of Producing Compound p-1 from Compound a-1

[0645] Compound p-1 can be produced from compound a-1 according to the process as described above in Producing Process 2, Step 1).

[0646] 2) Process of Producing Compound p-2 from Compound p-1 Compound p-2 can be produced by reacting compound p-1 with compound p-7 of the general formula: 41

[0647] wherein E25, E26, and R209 are as defined above, in a solvent in the presence of a base.

[0648] Amount of compound p-7: 0.9 to 10 moles relative to 1 mole of compound p-1

[0649] Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

[0650] Amount of base: 0.1 to 10 moles relative to 1 mole of compound p-1

[0651] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; and mixtures thereof; etc.

[0652] Reaction temperature: −40° C. to the reflux temperature of the solvent

[0653] Reaction time: a moment to 72 hours

[0654] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0655] Compound p-2 can also be used as such for the reaction in the next step without isolation.

[0656] 3) Process of Producing Compound p-3 from Compound p-2

[0657] Compound p-3 can be produced by reacting compound p-2 with compound o-6 of the general formula:

M9-E27  o-6

[0658] wherein E27 and M9 are as defined above, in a solvent in the presence of a base.

[0659] Amount of compound o-6: 0.9 to 10 moles relative to 1 mole of compound p-2

[0660] Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

[0661] Amount of base: 0.1 to 10 moles relative to 1 mole of compound p-2

[0662] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

[0663] Reaction temperature: −10° C. to the reflux temperature of the solvent

[0664] Reaction time: a moment to 72 hours

[0665] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0666] Producing Process 16

[0667] This is the producing process according to the following scheme: 42

[0668] wherein R1, R2, R3, R4, D7, E25 E26, E27, T A, and Y as defined above.

[0669] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 63-41466, or for example, by the following processes.

[0670] 1) Process of Producing Compound p-4 from Compound p-1

[0671] Compound p-4 can be produced by reacting compound p-1 with ammonia in a solvent.

[0672] Amount of ammonia: 1 mole to large excess relative to 1 mole of compound p-1

[0673] Solvent: water, methanol, ethanol, tetrahydrofuran, 1,4-dioxane, etc.

[0674] Reaction temperature: −20° C. to 100° C.

[0675] Reaction time: a moment to 24 hours

[0676] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0677] 2) Process of Producing Compound p-2 from Compound p-4

[0678] Compound p-2 can be produced by reacting compound p-4 with compound p-9 of the general formula: 43

[0679] wherein E25, E26, and R209 are as defined above and R210 is methyl, in a solvent in the presence of a base.

[0680] Amount of compound p-9: 0.9 to 10 moles relative to 1 mole of compound p-4

[0681] Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

[0682] Amount of base: 0.1 to 10 moles relative to 1 mole of compound p-4

[0683] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

[0684] Reaction temperature: room temperature to the reflux temperature of the solvent

[0685] Reaction time: a moment to 120 hours

[0686] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0687] Compound p-2 can also be used as such for the reaction in the next step without isolation.

[0688] 3) Process of Producing Compound p-3 from Compound p-2

[0689] Compound p-3 can be produced by reacting compound p-2 with compound o-6 of the general formula:

M9-E27  o-6

[0690] wherein E27 and M9 are as defined above, in a solvent in the presence of a base.

[0691] Amount of compound o-6: 0.9 to 10 moles relative to 1 mole of compound p-2

[0692] Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

[0693] Amount of base: 0.1 to 10 moles relative to 1 mole of compound p-2

[0694] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

[0695] Reaction temperature: −10° C. to the reflux temperature of the solvent

[0696] Reaction time: a moment to 72 hours

[0697] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0698] Producing Process 17

[0699] This is the producing process according to the following scheme: 44

[0700] wherein R1, R2, R3, R4, D7, E2, E29, A, T, and Y are as defined above.

[0701] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 6-92943, or for example, by the following processes.

[0702] 1) Process of Producing Compound p-6 from Compound p-5

[0703] Compound p-6 can be produced by reducing compound p-5 in a solvent.

[0704] Kind of reducing agent: NaBH4 etc.

[0705] Amount of reducing agent: 1 to 10 moles relative to 1 mole of compound p-5

[0706] Solvent: water, methanol, ethanol, acetic acid, etc.

[0707] Reaction temperature: −10° C. to the reflux temperature of the solvent

[0708] Reaction time: a moment to 48 hours

[0709] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound The compound can be purified by a technique such as recrystallization or column chromatography.

[0710] Producing Process 18

[0711] This is the producing process according to the following scheme: 45

[0712] wherein R1, R2, R3, R4, E30, E31, E42, T, A, andY are as defined above, and R211 is hydrogen, methyl, or ethyl.

[0713] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 9-323977 and WO98/17632, or for example, by the following processes.

[0714] 1) Process of Producing Compound w-1 from Compound a-1

[0715] Compound w-1 can be produced from compound a-1 according to the process as described above in Producing Process 5, Step 1).

[0716] 2) Process of Producing Compound w-2 from Compound w-1

[0717] Compound w-2 can be produced by reacting compound w-8 of the general formula: 46

[0718] wherein E30 and E42 are as defined above and M10 is iodine, bromine, or chlorine, with water in the presence of a base to form compound w-9 of the general formula: 47

[0719] wherein E30 and E42 are as defined above (reaction 1), and then reacting the carbonyl derivative with compound w-1 (reaction 2).

[0720] (Reaction 1)

[0721] Reaction 1 is usually carried out in a solvent. The reaction temperature is usually in the range of 20° C. to 100° C. The reaction time is usually in the range of a moment to 72 hours. The amounts of agents to be used in the reaction are 2 moles of each of the water and base relative to 1 mole compound w-8, which is ideal but can be freely changed depending upon the reaction conditions.

[0722] As the base to be used, both organic bases and inorganic bases can be used, examples of which are sodium acetate and potassium acetate.

[0723] The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate and butyl acetate; nitro compounds such as nitromethane and nitrobenzene; nitrites such as acetonitrile; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof.

[0724] (Reaction 2)

[0725] Reaction 2 is usually carried out in a solvent. The reaction temperature is usually in the range of-20° C. to 200° C. The reaction time is usually in the range of a moment to 72 hours. The amounts of agents to be used in the reaction are 1 mole of compound w-1 relative to 1 mole of compound w-8, which is ideal but can be freely changed depending upon the reaction conditions Depending upon the conditions, salts of compound w-1, such as hydrochloride salt and sulfate salt, can also be used.

[0726] The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate and butyl acetate; nitro compounds such as nitromethane and nitrobenzene; nitrites such as acetonitrile; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof.

[0727] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0728] 3) Process of Producing Compound w-3 from Compound w-2 (Route 1)

[0729] Compound w-3 can be produced by reacting compound w-2 with phosphorane compound w-10 of the general formula: 48

[0730] wherein E31 is as defined above; R213 is methyl or ethyl; and Ar is optionally substituted phenyl (e.g., phenyl), in a solvent.

[0731] This reaction is usually carried out in a solvent. The reaction temperature is usually in the range of −20° C. to 150° C., preferably 0° C. to 100° C. The reaction time is usually in the range of a moment to 72 hours. The amounts of agents to be used in the reaction are 1 mole of compound w-10 relative to 1 mole of compound w-2, which is ideal but can be freely changed depending upon the reaction conditions.

[0732] The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate and butyl acetate; nitro compounds such as nitromethane and nitrobenzene; nitriles such as acetonitrile; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof.

[0733] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0734] 4) Process of Producing Compound w-4 from Compound w-2 (Route 2)

[0735] Compound w-4 can be produced by reacting compound w-2 with compound w-11 of the general formula: 49

[0736] wherein E31 and R211 are as defined above, in the presence of a base.

[0737] This reaction is usually carried out in a solvent. The reaction temperature is usually in the range of 20° C. to 200° C., preferably 40° C. to 150° C. The reaction time is usually in the range of a moment to 72 hours. The amounts of agents to be used in the reaction are usually 1 to 10 moles of compound w-11, preferably 1 to 2 moles of compound w-11, which is ideal, relative to 1 mole of compound w-2. The amount of base is usually 1 mole to large excess, preferably 1 to 10 moles, relative to 1 mole of compound w-11

[0738] The base which can be used may include organic bases such as triethylamine and tributylamine.

[0739] The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate and butyl acetate; nitro compounds such as nitromethane and nitrobenzene; nitrites such as acetonitrile; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof.

[0740] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0741] 5) Process of Producing Compound w-3 from Compound w-4

[0742] Compound w-3 can be produced by reacting compound w-4, if necessary, in the presence of a base or acid, or in an acid-base mixed system.

[0743] This reaction is usually carried out in a solvent. The reaction temperature is usually in the range of 20° C. to 200° C., preferably 40° C. to 150° C. The reaction time is usually in the range of a moment to 96 hours.

[0744] The kind of base used, if necessary, may include organic bases such as pyridine; and metal alcoholates such as sodium methylate. The amount of base is usually 1 mole to large excess, preferably 1 to 10 moles, which is ideal, relative to 1 mole of compound w-4.

[0745] The kind of acid used, if necessary, may include organic acids such as acetic acid and benzoic acid; and p-toluenesulfonic acid. The amount of acid is usually 1 mole to large excess, preferably 1 to 10 moles, which is ideal, relative to 1 mole of compound w-4.

[0746] The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate and butyl acetate; nitro compounds such as nitromethane and nitrobenzene; nitrites such as acetonitrile; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; and mixtures thereof.

[0747] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0748] Compound w-7 (i.e., compound w-2 wherein E42 is H) can also be produced according to the following scheme: 50

[0749] wherein R1, R2, R3, R4, E30, T, A, and Y are as defined above, and R214 is methyl or ethyl.

[0750] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 9-323977, or for example, by the following processes.

[0751] 6) Process of Producing Compound w-5 from Compound a-1 (see Tetrahedron, vol. 35, p. 2013 (1979))

[0752] Compound w-5 can be produced by converting compound a-1 into a diazonium salt with sodium nitrite in a solvent in the presence of an acid, and then reacting the diazonium salt with compound w-12 of the general formula: 51

[0753] wherein E30 and R214 are as defined above, in a solvent in the presence of a base.

[0754] (Diazonium Salt Formation)

[0755] Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound a-1

[0756] Kind of acid: hydrochloric acid etc.

[0757] Amount of acid: 1 to 100 moles relative to 1 mole of compound a-1

[0758] Solvent: water, ethanol, hydrochloric acid, etc.

[0759] Reaction temperature: −15° C. to room temperature

[0760] Reaction time: a moment to 24 hours

[0761] (Reaction with Compound w-12)

[0762] Amount of compound w-12: 1 to 5 moles relative to 1 mole of compound a-1

[0763] Kind of base: sodium acetate etc.

[0764] Amount of base: 0.8 to 3 moles relative to 1 mole of acid used in the forgoing step

[0765] Solvent: ethanol, water, etc.

[0766] Reaction temperature: 0° C. to 60° C.

[0767] Reaction time: a moment to 48 hours

[0768] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0769] 6) Process of Producing Compound w-6 from Compound w-5

[0770] Compound w-6 can be produced by reacting compound w-5 in a solvent in the presence of a base.

[0771] The reaction temperature is usually in the range of 0° C. to 150° C. The reaction time is usually in the range of a moment to 72 hours. The amounts of agents to be used in the reaction are 1 mole of base relative to 1 mole of compound w-5, which is ideal but can be freely changed, if necessary. The base may include inorganic bases such as sodium hydroxide, lithium hydroxide, lithium hydroxide monohydrate, barium hydroxide, and potassium hydroxide.

[0772] The solvent which, can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; nitriles such as acetonitrile; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof.

[0773] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0774] 7) Process of Producing Compound w-7 from Compound w-6

[0775] Compound w-7 can be produced by heating compound w-6 in a solvent.

[0776] The reaction temperature is usually in the range of 50° C. to 200° C. The reaction time is usually in the range of a moment to 72 hours.

[0777] The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; nitriles such as acetonitrile; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol and isopropanol; nitrogen-containing aromatic compounds such as pyridine and picoline; sulfur compounds such as dimethylsulfoxide; tertiary amines such as N,N-dimethylaniline; water; and mixtures thereof.

[0778] In this reaction, metals such as copper powder may be used as a catalyst, if necessary.

[0779] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0780] Producing Process 19

[0781] This is the producing process according to the following scheme: 52

[0782] wherein R1, R2, R3, R4, E32, E33, E43, T, A, and Y are as described above.

[0783] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 6-25186, or for example, by the following processes.

[0784] 1) Process of Producing Compound r-1 from Compound a-1

[0785] Compound r-1 can be produced by converting compound a-1 into an isothiocyanate derivative in a solvent or without solvent.

[0786] Agent for conversion into isothiocyanate derivatives: thiophosgene etc.

[0787] Amount of agent for conversion into isothiocyanate derivatives: 1 equivalent to an excess amount relative to 1 mole of compound a-1

[0788] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; etc.

[0789] Reaction temperature: room temperature to the reflux temperature of the solvent

[0790] Reaction time: a moment to 96 hours

[0791] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0792] 2) Process of Producing Compound r-2 from Compound r-1

[0793] Compound r-2 can be produced by reacting compound r-1 with compound r-6 of the general formula: 53

[0794] wherein E32 and E43 are as defined above and R215 is methyl, ethyl, or propyl in a solvent in the presence of a base.

[0795] Amount of compound r-6: 0.9 to 10 moles relative to 1 mole of compound r-1

[0796] Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

[0797] Amount of base: 0.1 to 10 moles relative to 1 mole of compound r-1

[0798] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

[0799] Reaction temperature: −10° C. to the reflux temperature of the solvent

[0800] Reaction time: a moment to 72 hours

[0801] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0802] 3) Process of Producing Compound r-3 from Compound r-2

[0803] Compound r-3 can be produced by reacting compound r-2 with Raney nickel in a solvent in the presence of a base.

[0804] Amount of Raney nickel: 1 to 20 moles relative to 1 mole of compound r-2

[0805] Kind of base: nitrogen-containing compounds such as pyridine; organic bases such as triethylamine; ammonia; etc.

[0806] Amount of base: 0.1 to 20 moles relative to compound r-2

[0807] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; alcohols such as methanol and ethanol; water; and mixtures thereof; etc.

[0808] Reaction temperature: −10° C. to the reflux temperature of the solvent Reaction time: a moment to 72 hours After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography. 4) Process of Producing Compound r-4 from Compound r-3

[0809] Compound r-4 can be produced by reacting compound r-3 in a solvent in the presence of a base.

[0810] Kind of base: metal alcoholates such as sodium methylate and sodium ethylate; etc.

[0811] Amount of base: 1 to 20 moles relative to compound r-3 Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; alcohols such as methanol and ethanol; water; and mixtures thereof; etc.

[0812] Reaction temperature: 20° C. to the reflux temperature of the solvent

[0813] Reaction time: a moment to 96 hours

[0814] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0815] 5) Process of Producing Compound r-5 from Compound r-4

[0816] Compound r-5 can be produced by reacting compound r-4 with an acylating agent selected from compound r-7 of the general formula: 54

[0817] wherein E33 is as defined above, or compound r-8 of the general formula: 55

[0818] wherein E33 is as defined above, in a solvent.

[0819] Amount of acylating agent: 1 to 5 moles relative to 1 mole of compound r-4

[0820] Solvent: organic acids such as acetic acid and propionic acid; etc.

[0821] Reaction temperature: the reflux temperature of the solvent

[0822] Reaction time: a moment to 96 hours

[0823] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0824] Producing Process 20

[0825] This is the producing process according to the following scheme: 56

[0826] wherein R1, R2, R3, R4, E34, T, A, and Y are as defined above.

[0827] The reaction can be carried out, for example, according to the process as described in JP-A 4-356463, or for example, by the following process.

[0828] 1) Process of Producing Compound s-1 from Compound a-1

[0829] Compound s-1 can be produced by reacting compound a-1 with acid anhydride s-2 of the general formula: 57

[0830] wherein E34 is as defined above, in a solvent, if necessary, in the presence of an acid.

[0831] Amount of acid anhydride s-2: 1 to 5 moles relative to 1 mole of compound a-1

[0832] Solvent: organic acids such as acetic acid and propionic acid; aromatic hydrocarbons such as benzene and toluene; etc.

[0833] Kind of acid: p-toluenesulfonic acid etc.

[0834] Reaction temperature: room temperature to the reflux temperature of the solvent

[0835] Reaction time: a moment to 96 hours

[0836] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0837] Producing Process 21

[0838] This is the producing process according to the following scheme: 58

[0839] wherein R1, R2, R3, R4, D9, V1, T, A, and Y are as defined above.

[0840] The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 5-25173, or for example, by the following processes.

[0841] 1) Process of Producing Compound t-1 from Compound a-1

[0842] Compound t-1 can be produced from compound a-1 according to the process as described above in Producing Process 2, Step 1).

[0843] 2) Process of Producing Compound t-2 from Compound t-1

[0844] Compound t-2 can be produced by reacting compound t-1 with compound t-3 of the general formula: 59

[0845] wherein V1 is as defined above, in a solvent in the presence of a base.

[0846] Amount of compound t-3: 0.9 to 10 moles relative to 1 mole of compound t-1

[0847] Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

[0848] Amount of base: 0.1 to 10 moles relative to 1 mole of compound t-1

[0849] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; and mixtures thereof; etc.

[0850] Reaction temperature: −40° C. to the reflux temperature of the solvent

[0851] Reaction time: a moment to 72 hours

[0852] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0853] Producing Process 22

[0854] This is the producing process according to the following schemes: 60 61

[0855] wherein R1, R2, R3, R4, E35, A, T, and Y are as defined above.

[0856] The reactions in the respective steps can be carried out, for example, according to the processes as described in WO98/14452, or for example, by the following processes.

[0857] 1) Process of Producing Compound u-1 from Compound a-1

[0858] Compound u-1 can be produced from compound a-1 according to the process as described above in Producing Process 19, Step 1).

[0859] 2) Process of Producing Compound u-2 from Compound u-1

[0860] Compound u-2 can be produced by reacting compound u-1 with compound u-12 of the general formula: 62

[0861] wherein E35 and R215 are as defined above, in a solvent in the presence of a base.

[0862] Amount of compound u-12: 0.9 to 10 moles relative to 1 mole of compound u-1

[0863] Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

[0864] Amount of base: 0.1 to 10 moles relative to 1 mole of compound u-1

[0865] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; and mixtures thereof; etc.

[0866] Reaction temperature: −10° C. to the reflux temperature of the solvent

[0867] Reaction time: a moment to 72 hours

[0868] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0869] 3) Process of Producing Compound u-3 from Compound u-2

[0870] Compound u-3 can be produced by reacting compound u-2 with a methylating agent such as methyl iodide or dimethyl sulfate in a solvent in the presence of a base.

[0871] Kind of base: organic bases such as triethylamine; nitrogen-containing compounds such as pyridine; inorganic bases such as sodium hydride, potassium carbonate, and potassium hydroxide; etc.

[0872] Amount of base: 1 to 20 moles relative to 1 mole of compound u-2

[0873] Amount of methylating agent: 1 to 20 moles relative to 1 mole of compound u-2

[0874] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran; amides such as N,N-dimethylformamide; water; and mixtures thereof; etc.

[0875] Reaction temperature: −10° C. to room temperature

[0876] Reaction time: a moment to 96 hours

[0877] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0878] 4) Process of Producing Compound u-4 from Compound u-3

[0879] Compound u-4 can be produced by reacting compound u-3 with an oxidizing agent in a solvent.

[0880] Kind of oxidizing agent: m-chloroperbenzoic acid, aqueous hydrogen peroxide, etc.

[0881] Amount of oxidizing agent: 2 to 20 moles relative to 1 mole of compound u-3

[0882] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated aliphatic hydrocarbons such as chloroform; water; and mixtures thereof; etc.

[0883] Reaction temperature: −20° C. to room temperature

[0884] Reaction time: a moment to 96 hours

[0885] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0886] 5) Process of Producing Compound u-5 from Compound u-4

[0887] Compound u-5 can be produced by reacting compound u-4 with ammonia in a solvent.

[0888] Amount of ammonia: 1 mole to large excess relative to 1 mole of compound u-4

[0889] Solvent: t-butanol, isopropanol, etc.

[0890] Reaction temperature: −20° C. to 40° C.

[0891] Reaction time: a moment to 10 hours

[0892] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0893] 6) Process of Producing Compound u-6 from Compound u-4

[0894] Compound u-6 can be produced by reacting compound u-4 with an azidizing agent such as sodium azide or trimethylsilyl azide in a solvent such as methanol, ethanol, and water.

[0895] Amount of azidizing agent: 1 equivalent to an excess amount relative to 1 mole of compound u-4

[0896] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0897] 7) Process of Producing Compound u-7 from Compound u-5

[0898] Compound u-7 can be produced by reacting compound u-5 with a haloacetaldehyde such as chloroacetaldehyde (40% aqueous solution) in a solvent.

[0899] The amount of haloacetaldehyde is 1 equivalent to an excess amount relative to 1 mole of compound u-5: The solvent may include ethers such as 1,4-dioxane and tetrahydrofuran; water; and mixtures thereof; etc. The reaction temperature is in the range of 40° C. to the reflux temperature of the solvent. The reaction time is in the range of a moment to 20 hours.

[0900] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0901] 8) Process of Producing Compound u-8 from Compound u-4

[0902] Compound u-8 can be produced by reacting compound u-4 with hydrazine (hydrate) in a solvent or without solvent.

[0903] Amount of hydrazine: 1 mole to a large excess amount relative to 1 mole of compound u-4

[0904] Solvent: t-butanol, isopropanol, etc.

[0905] Reaction temperature: −20° C. to 40° C.

[0906] Reaction time: a moment to 10 hours

[0907] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0908] 9) Process of Producing Compound u-9 from Compound u-4

[0909] Compound u-9 can be produced by reacting compound u-4 with 2-ethanolamine in a solvent or without solvent.

[0910] Amount of 2-ethanolamine: 1 mole to a large excess amount relative to 1 mole of compound u-4

[0911] Solvent: t-butanol, isopropanol, etc.

[0912] Reaction temperature: −20° C. to 40° C.

[0913] Reaction time: a moment to 10 hours

[0914] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0915] 10) Process of Producing Compound u-10 from Compound u-8

[0916] Compound u-10 can be produced by reacting compound u-8 with formic acid in a solvent or without solvent, if necessary, in the presence of another acid.

[0917] Kind of acid: p-toluenesulfonic acid, hydrochloric acid, etc.

[0918] Amount of acid: 0.001 mole to a large excess amount relative to 1 mole of compound u-8

[0919] Amount of formic acid: 1 mole to a large excess amount to 1 mole of compound u-8

[0920] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N-N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; alcohols such as methanol and ethanol; water; and mixtures thereof; etc.

[0921] Reaction temperature: 40° C. to the reflux temperature of the solvent

[0922] Reaction time: a moment to 10 hours

[0923] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0924] 11) Process of Producing Compound u-11 from Compound u-9

[0925] Compound u-11 can be produced by reacting compound u-9 in a solvent or without solvent in the presence of an acid.

[0926] Kind of acid: p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, polyphosphoric acid, etc.

[0927] Amount of acid: 0.001 mole to a large excess amount relative to 1 mole of compound u-9

[0928] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N-N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; alcohols such as methanol and ethanol; water; and mixtures thereof; etc.

[0929] Reaction temperature: 40° C. to the reflux temperature of the solvent

[0930] Reaction time: a moment to 48 hours

[0931] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystaliization or column chromatography.

[0932] Producing Process 23

[0933] This is the producing process according to the following scheme: 63

[0934] wherein R1, R2, R3, R4, R215, E32, E33, E43, T, A, and Y are as defined above; and R216 is C1-C5 alkoxy (e.g., methoxy, ethoxy) or NR217(R218) (e.g., dimethylamino, diethylamino) wherein R217 and R218 are independently C1-C5 alkyl.

[0935] The reactions in the respective steps can be carried out, for example, according to the processes as described in Bull. Soc. Chim. Fr. (134, pp. 47-57, 1997), or for example, by the following processes.

[0936] 1) Process of Producing Compound r-9 from Compound r-6

[0937] Compound r-9 can be produced by reacting compound r-6 with compound r-10 of the general formula: 64

[0938] wherein E33 and R216 are as defined above; R219 and R220 are independently C1-C5 alkyl (e.g., methyl, ethyl), in a solvent, if necessary, in the presence of an acid.

[0939] Amount of compound r-10: 1 mole to an excess amount relative to 1 mole of compound r-6

[0940] Kind of acid: organic acids such as acetic acid and p-toluenesulfonic acid

[0941] Amount of acid: a catalytic amount to large excess relative to 1 mole of compound r-6

[0942] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof, etc.

[0943] Reaction temperature: 10° C. to the reflux temperature of the solvent

[0944] Reaction time: a moment to 96 hours

[0945] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0946] 2) Process of Producing Compound r-5 from Compound r-9

[0947] Compound r-5 can be produced by reacting compound r-9 with compound a-1 in a solvent, if necessary, in the presence of an acid.

[0948] Amount of compound a-1: 0.9 to 1.1 moles relative to 1 mole of compound r-9

[0949] Kind of acid: organic acids such as acetic acid and p-toluenesulfonic acid

[0950] Amount of acid: a catalytic amount to large excess relative to 1 mole of compound r-9

[0951] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

[0952] Reaction temperature: 10° C. to the reflux temperature of the solvent

[0953] Reaction time: a moment to 96 hours

[0954] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0955] Depending upon the kinds of R1, R2, R3, R4, Y, T and A, the formation of Q may be followed by the introduction or formation of R1, R2, R3, R4, Y, T, and A. In these producing processes, protective groups may be used, if necessary, for the protection of functional groups from the reactions. (see “Protective Groups in Organic Synthesis” written by T. W. Greene.) The following are examples of these producing processes.

[0956] Producing Process 24

[0957] This is the producing process according to the following scheme: 65

[0958] wherein R1, R2, R3, R4, Y11, and Q are as defined above; R221 is methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, aminocarbonyl, or nitrile; and M23 is fluorine, chlorine, or bromine. The reactions in the respective steps can be carried out, for example, by the following processes.

[0959] 1) Process of Producing Compound z-2 from Compound z-1

[0960] Compound z-2 can be produced by reacting with compound z-1 in a solvent in the presence of a base or acid, and, if necessary, in the presence of a phase transfer catalyst.

[0961] Kind of base: inorganic bases such as sodium hydroxide, potassium hydroxide, and lithium hydroxide; etc.

[0962] Amount of base: 0.9 to 10 moles relative to 1 mole of compound z-1

[0963] Kind of acid: hydrochloric acid, sulfuric acid, etc.

[0964] Amount of acid: 1 mole to an excess amount relative to 1 mole of compound z-1

[0965] Kind of phase transfer catalyst: tetrabutylammonium bromide etc.

[0966] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

[0967] Reaction temperature: 10° C. to the reflux temperature of the solvent

[0968] Reaction time: a moment to 96 hours

[0969] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0970] 2) Process of Producing Compound z-3 from Compound z-2

[0971] Compound z-3 can be produced by heating compound z-2 in a solvent, if necessary, in the presence of an acid or base.

[0972] Kind of base: nitrogen-containing compounds such as quinoline and pyridine; amides such as N,N-dimethylformamide; sulfur compounds such as sulforane; aromatic hydrocarbons such as xylene and mesitylene; and mixtures thereof; etc.

[0973] Amount of base: 0.9 mole to an excess amount relative to 1 mole of compound z-2

[0974] Kind of acid: hydrochloric acid, sulfuric acid, etc.

[0975] Amount of acid: 1 mole to an excess amount relative to 1 mole of compound z-2

[0976] Kind of phase transfer catalyst: tetrabutylammonium bromide etc.

[0977] Solvent: amides such as N,N-dimethylformamide; sulfur compounds such as sulforane; aromatic hydrocarbons such as xylene and mesitylene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; and mixtures thereof; etc.

[0978] Reaction temperature: 50° C. to the reflux temperature of the solvent

[0979] Reaction time: a moment to 96 hours

[0980] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0981] In this process, metal catalysts such as copper may be used in their catalytic amounts.

[0982] 3) Process of Producing Compound z-24 from Compound z-23

[0983] Compound z-24 can be produced by reducing compound z-23 with iron powder in a solvent.

[0984] Amount of iron powder: 2 to 10 moles relative to 1 mole of compound z-23

[0985] Solvent: acetic acid, water, and mixtures thereof, etc.

[0986] Reaction temperature: 15° C. to 110° C.

[0987] Reaction time: a moment to 100 hours

[0988] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[0989] 4) Process of Producing Compound z-25 from Compound z-24

[0990] Compound z-25 can be produced by converting compound z-24 into a diazonium salt with sodium nitrite in the presence of an acid and then reacting the diazonium salt with copper halide such as copper (I) chloride or copper (I) bromide.

[0991] (Diazonium Salt Formation)

[0992] Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound z-24

[0993] Kind of acid: sulfuric acid, hydrochloric acid, etc.

[0994] Amount of acid: 1 mole to 100 moles relative to 1 mole of compound z-24

[0995] Solvent: water, ethanol, hydrochloric acid, etc.

[0996] Reaction temperature: −15° C. to room temperature

[0997] Reaction time: a moment to 24 hours

[0998] (Reaction with Copper Halide)

[0999] Kind of copper halide: copper (I) chloride, copper (I) bromide, etc.

[1000] Amount of copper halide: 1 to 10 moles relative to 1 mole of compound z-24

[1001] Solvent: hydrochloric acid, hydrobromic acid, etc.

[1002] Reaction temperature: −10° C. to 80° C.

[1003] Reaction time: a moment to 48 hours

[1004] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1005] 5) Process of Producing Compound z-3 from Compound z-24 Compound z-3 can be produced by converting compound z-24 into a diazonium salt with sodium nitrite in the presence of an acid and then reacting the diazonium salt in a solvent.

[1006] (Diazonium Salt Formation)

[1007] Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound z-24

[1008] Kind of acid: sulfuric acid, hydrochloric acid, etc.

[1009] Amount of acid: 1 mole to 100 moles relative to 1 mole of compound z-24

[1010] Solvent: water, ethanol, hydrochloric acid, etc.

[1011] Reaction temperature: −15° C. to room temperature

[1012] Reaction time: a moment to 24 hours

[1013] (Thermal Decomposition)

[1014] Solvent: sulfuric acid, water, etc.

[1015] Reaction temperature: room temperature to 200° C.

[1016] Reaction time: a moment to 48 hours

[1017] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1018] Producing Process 25

[1019] This is the producing process according to the following scheme: 66

[1020] wherein R1, R3, R4, R11, Q, T, A, and Y are as defined above.

[1021] The reactions in the respective steps can be carried out, for example, by the following processes.

[1022] 1) Process of Producing Compound z-5 from Compound z-4

[1023] Compound z-5 can be produced by demethylating compound z-4 in a solvent in the presence of an acid or trimethylsilane iodide.

[1024] Kind of acid: inorganic acids such as hydrochloric acid and sulfuric acid; Lewis acids such as boron tribromide and aluminum chloride; etc.

[1025] Amount of acid: 1 mole to an excess amount relative to 1 mole of compound z-4

[1026] Amount of trimethylsilane iodide: 1 mole to an excess amount relative to 1 mole of compound z-4

[1027] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated hydrocarbons such as chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

[1028] Reaction temperature: 0° C. to the reflux temperature of the solvent

[1029] Reaction time: a moment to 168 hours

[1030] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1031] 2) Process of Producing Compound z-6 from Compound z-5

[1032] Compound z-6 can be produced by reacting compound z-5 with compound z-18 of the general formula:

M9-R11  z-18

[1033] wherein M9 and R11 are as defined above, in a solvent in the presence of a base.

[1034] Amount of compound z-18: 1 to 2 moles relative to 1 mole of compound z-5

[1035] Kind of base: potassium carbonate, sodium hydride, etc.

[1036] Amount of base: 1 to 5 moles relative to 1 mole of compound z-5

[1037] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated hydrocarbons such as chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

[1038] Reaction temperature: −10° C. to 100° C.

[1039] Reaction time: a moment to 48 hours

[1040] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1041] Producing Process 26

[1042] This is the producing process according to the following scheme: 67

[1043] wherein R1, R4, Q, T, A, and Y are as defined above, R222 is —OR11 or —SR12 wherein R11 and R12 are as defined above; and R223 is —OR224 or —SR225 wherein R224 and R225 are the same or different and independently hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C1-C10 alkenyl, C3-C10 alkynyl, C1-C5 alkoxy C1-C5 alkyl, C1-C5 alkylthio C1-C5 alkyl, or optionally substituted phenyl.

[1044] The reactions in the respective steps can be carried out, for example, by the following processes.

[1045] 1) Process of Producing Compound z-8 from Compound z-7

[1046] Compound z-8 can be produced by reacting compound z-19 of the general formula:

H-R222  z-19

[1047] wherein R222 is as defined above, in a solvent in the presence of a base.

[1048] Amount of compound z-19: 1 to 5 moles relative to 1 mole of compound z-7

[1049] Kind of base: organic bases such as triethylamine, inorganic bases such as potassium carbonate and sodium hydride; alkoxides such as sodium methoxide and sodium thiomethoxide; etc.

[1050] Amount of base: 1 to 5 moles relative to 1 mole of compound z-7

[1051] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated hydrocarbons such as chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

[1052] Reaction temperature: −10° C. to the reflux temperature of the solvent

[1053] Reaction time: a moment to 72 hours

[1054] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1055] Compound z-8 wherein R222 is —OR224 or —SR225; and R224 and R225 are as defined above (hereinafter referred to as compound z-8′) can be used to produce compound z-9 or compound z-10 as shown in the following processes.

[1056] 2) Process of Producing Compound z-9 from Compound z-8′

[1057] Compound z-9 can be produced by reducing compound z-8′ with iron powder in a solvent.

[1058] Amount of iron powder: 2 to 10 moles relative to 1 mole of compound z-8′

[1059] Solvent: acetic acid, water, and mixtures thereof; etc.

[1060] Reaction temperature: 15° C. to 110° C.

[1061] Reaction time: a moment to 100 hours

[1062] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1063] 3) Process of Producing Compound z-10 from Compound z-9

[1064] Compound z-10 can be produced by converting compound z-9 into a diazonium salt with sodium nitrite in the presence of an acid and then reacting the diazonium salt with a chloride such as copper (I) chloride.

[1065] (Diazonium Salt Formation)

[1066] Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound z-9

[1067] Kind of acid: hydrochloric acid, etc.

[1068] Amount of acid: 1 mole to 100 moles relative to 1 mole of compound z-9

[1069] Solvent: water, ethanol, hydrochloric acid, etc.

[1070] Reaction temperature: −15° C. to room temperature

[1071] Reaction time: a moment to 24 hours

[1072] (Reaction with Chloride)

[1073] Kind of chloride: copper (I) chloride etc.

[1074] Amount of chloride: 1 to 10 moles relative to 1 mole of compound z-9

[1075] Solvent: hydrochloric acid etc.

[1076] Reaction temperature: −10° C. to 80° C.

[1077] Reaction time: a moment to 48 hours

[1078] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1079] Producing Process 27

[1080] This is the producing process according to the following process: 68

[1081] wherein R1, R3, R4, R14, R17, R19, Q, T, A, and Y are as defined above.

[1082] The reactions in the respective steps can be carried out, for example, by the following processes.

[1083] 1) Process of Producing Compound z-12 from Compound z-11

[1084] Compound z-12 can be produced by reacting compound z-11 with copper (I) cyanide in a solvent.

[1085] Amount of copper (1) cyanide: 1 to 4 moles relative to 1 mole of compound z-11

[1086] Kind of solvent: amides such as N,N-dimethylformamide and N-methylpyrrolidone; sulfur compound such as dimethylsulfoxide; etc.

[1087] Reaction temperature: 40° C. to the reflux temperature of the solvent

[1088] Reaction time: a moment to 120 hours

[1089] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1090] 2) Process of Producing Compound z-13 from Compound z-12

[1091] Compound z-13 can be produced by reacting compound z-12 with water in the presence of an acid.

[1092] Amount of water: 1 mole to an excess amount relative to 1 mole of compound z-12

[1093] Kind of acid: hydrochloric acid, sulfuric acid, etc.

[1094] Amount of acid: 1 mole to an excess amount relative to 1 mole of compound z-12

[1095] Reaction temperature: 10° C. to 50° C.

[1096] Reaction time: a moment to 24 hours

[1097] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1098] 3) Process of Producing Compound z-14 from Compound z-13

[1099] Compound z-14 can be produced by reacting compound z-13 with water in the presence of an acid or base.

[1100] Amount of water: 1 equivalent to an excess amount relative to 1 mole of compound z-13

[1101] Kind of acid: hydrochloric acid, sulfuric acid, etc.

[1102] Amount of acid: 1 equivalent to an excess amount relative to 1 mole of compound z-13

[1103] Kind of base: sodium hydroxide, potassium hydroxide, etc.

[1104] Amount of base: 1 to 3 equivalents relative to 1 mole of compound z-13

[1105] Reaction temperature: room-temperature to 150° C.

[1106] Reaction time: a moment to 120 hours

[1107] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1108] 4) Process of Producing Compound z-17 from Compound z-14

[1109] Compound z-17 can be produced by reacting compound z-14 with thionyl chloride to form an acid chloride compound (reaction 1) and then reacting the acid chloride compound with compound z-20 of the general formula:

HO—R14  z-20

[1110] wherein R14 is as defined above, in a solvent in the presence of a base (reaction 2).

[1111] (Reaction 1)

[1112] Amount of thionyl chloride: 1 mole to an excess amount relative to compound z-14

[1113] Reaction temperature: 40° C. to the reflux temperature of thionyl chloride

[1114] Reaction time: a moment to 10 hours

[1115] After completion of the reaction, the reaction mixture was concentrated and used as the starting material for reaction 2.

[1116] (Reaction 2)

[1117] Amount of compound z-20: 1 mole to an excess amount relative to 1 mole of compound z-14

[1118] Kind of base: pyridine, triethylamine, potassium carbonate, etc.

[1119] Amount of base: 1 to 5 moles relative to 1 mole of compound z-14

[1120] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated hydrocarbons such as chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

[1121] Reaction temperature: −10° C. to the reflux temperature of the solvent

[1122] Reaction time: a moment to 120 hours

[1123] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1124] 5) Process of Producing Compound z-17 from Compound z-13

[1125] Compound z-17 can be produced by reacting compound z-13 with compound z-20 of the general formula:

HO—R14z-20

[1126] wherein R14 is as defined above, in a solvent in the presence of a boron trihalide compound.

[1127] Amount of compound z-20: 1 mole to an excess amount relative to 1 mole of compound z-13

[1128] Kind of boron trihalide compound: boron trifluoride, boron trichloride, boron tribromide, etc.

[1129] Amount of boron trihalide compound: 1 mole to an excess amount relative to 1 mole of compound z-13

[1130] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof, etc.

[1131] Reaction temperature: 50° C. to the reflux temperature of the solvent

[1132] Reaction time: a moment to 120 hours

[1133] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1134] 6) Process of Producing Compound z-15 from Compound z-12

[1135] Compound z-15 can be produced by reacting compound z-12 with compound z-21 of the general formula:

M11-Mg—R17  z-21

[1136] wherein R17 is as defined above and M11 is chlorine or bromine, in a solvent.

[1137] Amount of compound z-21: 1 to 1.3 moles relative to 1 mole of compound z-12

[1138] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated hydrocarbons such as chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

[1139] Reaction temperature: 0° C. to the reflux temperature of the solvent

[1140] Reaction time: a moment to 48 hours

[1141] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1142] 7) Process of Producing Compound z-16 from Compound z-15

[1143] Compound z-16 can be produced by reacting compound z-15 with compound z-22 of the general formula:

R19ONH2  z-22

[1144] wherein R19 is as defined above, in a solvent, if necessary, in the presence of a base.

[1145] Amount of compound z-22: 1 to 3 moles relative to 1 mole of compound z-15

[1146] Kind of base: triethylamine, pyridine, potassium carbonate, etc.

[1147] Amount of base: 1 to 5 moles relative to 1 mole of compound z-15

[1148] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

[1149] Reaction temperature: 0° C. to the reflux temperature of the solvent

[1150] Reaction time: a moment to 120 hours

[1151] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1152] In addition to the above processes, the present compounds can also be produced by making reference to, for example, JP-A 5-213970, EP 683160-A1, and JP-A 61-161288.

[1153] The processes of producing some of the starting materials used in the production of the present compounds are explained below.

[1154] Reference Producing Process 1

[1155] This is the producing process according to the following scheme: 69

[1156] wherein R1, R2, R3, R4, and Y11 are as defined above; and R250 is carboxy, methoxycarbonyl, ethoxycarbonyl, aminocarbonyl, or nitrile.

[1157] The reactions in the respective steps can be carried out, for example, according to the processes as described in Indian Journal of Chemistry (vol. 20B, pp. 391-393, 1981), Indian Journal of Chemistry (vol. 14B, pp. 6886-6891, 1981), Organic Syntheses (vol. 33, p. 43, 1953), or for example, by the following processes.

[1158] 1) Process of Producing Compound v-2 from Compound v-1

[1159] Compound v-2 can be produced by reacting compound v-1 with compound v-19 of the general formula: 70

[1160] wherein R250 is as defined above and M20 is chlorine, bromine, or iodine, in a solvent in the presence of a base.

[1161] Kind of base: inorganic bases such as potassium carbonate, sodium hydride, and sodium hydroxide; organic bases such as triethylamine; nitrogen-containing compounds such as pyridine; metal alcoholates such as sodium methylate and sodium ethylate; etc.

[1162] Amount of base: 1 to 5 moles relative to 1 mole of compound v-1 Amount of compound v-19: 0.9 to 3 moles relative to 1 mole of compound v-1

[1163] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ketones such as acetone; ethers such as tetrahydrofuran; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

[1164] Reaction temperature: 0° C. to the reflux temperature of the solvent

[1165] Reaction time: a moment to 48 hours

[1166] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1167] 2) Process of Producing Compound v-3 from Compound v-2

[1168] Compound v-3 can be produced by reacting compound v-2 in a solvent in the presence of a base.

[1169] Kind of base: inorganic bases such as potassium carbonate, sodium hydride, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

[1170] Amount of base: 1 to 10 moles relative to 1 mole of compound v-2

[1171] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

[1172] Reaction temperature: 10° C. to the reflux temperature of the solvent

[1173] Reaction time: a moment to 96 hours

[1174] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1175] 3) Process of Producing Compound v-4 from Compound v-3

[1176] Compound v-4 can be produced by reacting compound v-3 in a solvent in the presence of a base or acid and, if necessary, in the presence of a phase transfer catalyst.

[1177] Kind of base: inorganic bases such as sodium hydroxide and potassium hydroxide; etc.

[1178] Amount of base: 0.9 to 10 moles relative to 1 mole of compound v-3

[1179] Kind of acid: hydrochloric acid, sulfuric acid, etc.

[1180] Amount of acid: 1 mole to an excess amount relative to 1 mole of compound v-3

[1181] Kind of phase transfer catalyst: tetrabutylammonium bromide etc.

[1182] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

[1183] Reaction temperature: 10° C. to the reflux temperature of the solvent

[1184] Reaction time: a moment to 96 hours

[1185] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1186] 4) Process of Producing Compound v-5 from Compound v-4

[1187] Compound v-5 can be produced by heating compound v-4 in a solvent, if necessary, in the presence of a base or acid.

[1188] Kind of base: nitrogen-containing compounds such as quinoline and pyridine; amides such as N,N-dimethylformamide; sulfur compounds such as sulforane; aromatic hydrocarbons such as xylene and mesitylene; and mixtures thereof; etc.

[1189] Amount of base: 0.9 mole to an excess amount relative to 1 mole of compound v-4 Kind of acid: hydrochloric acid, sulfuric acid, etc.

[1190] Amount of acid: 1 mole to an excess amount relative to 1 mole of compound v-4

[1191] Solvent: amides such as N,N-dimethylformamide; sulfur compounds such as sulforane; aromatic hydrocarbons such as xylene and mesitylene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; and mixtures thereof; etc.

[1192] Reaction temperature: 50° C. to the reflux temperature of the solvent

[1193] Reaction time: a moment to 96 hours

[1194] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1195] In this process, metal catalysts such as copper may be used.

[1196] Compound v-1 as the starting material in this producing process can also be produced from the corresponding benzaldehyde derivative by making reference to, for example, Shin Jikken Kagaku Koza (published by Maruzen Kabushiki Kaisha) vol. 14, pp. 1466-1470. The benzaldehyde derivative to be used as the starting material at that time can also be produced by making reference to, for example, EP 0312338-A1, Synthetic Communication, 24(12), pp. 1757-1760 (1994), and J. Chem. Soc. Perkin I, pp. 318-321 (1978).

[1197] Compound v-2 as the intermediate can also be produced according to the following scheme 1 or 2. 71

[1198] wherein R1, R2, R3, R4, R250, and Y11 are as defined above; and M21 is fluorine, chlorine, or bromine.

[1199] 5) Process of Producing Compound v-2 from Compound v-6

[1200] Compound v-2 can be produced by reacting compound v-6 with compound v-17 of the formula: 72

[1201] wherein Y11 and R250 are as defined above, in a solvent in the presence of a base.

[1202] Kind of base: inorganic bases such as potassium carbonate, sodium hydride, sodium hydroxide, and potassium fluoride; organic bases such as triethylamine; nitrogen-containing compounds such as pyridine; etc.

[1203] Amount of base: 1 to 10 moles relative to 1 mole of compound v-6

[1204] Amount of compound v-17: 0.9 to 10 moles relative to 1 mole of compound v-6

[1205] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ketones such as acetone; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; and mixtures thereof; etc.

[1206] Reaction temperature: 0° C. to the reflux temperature of the solvent

[1207] Reaction time: a moment to 72 hours

[1208] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography. 73

[1209] wherein R1, R2, R3, R4, R250, and Y11 are as defined above.

[1210] 1) Process of Producing Compound v-2 from Compound v-16

[1211] Compound v-2 can be produced by reacting compound v-16 with copper (I) cyanide in a solvent.

[1212] Amount of copper (I) cyanide: 1 to 4 moles relative to 1 mole of compound v-16

[1213] Kind of solvent: amides such as N,N-dimethylformamide and N-methylpyrrolidone; sulfur compound such as dimethylsulfoxide; etc.

[1214] Reaction temperature: 40° C. to the reflux temperature of the solvent

[1215] Reaction time: a moment to 120 hours

[1216] After completion of the reaction, ammonia water is added, if necessary, to the reaction mixture, which is then extracted with an organic solvent, and the organic layer is dried and concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1217] Reference Producing Process 2

[1218] This is the producing process according to the following scheme: 74

[1219] wherein R1, R2, R3, and R4 are is defined above; and M22 is fluorine or chlorine.

[1220] The reactions in the respective steps can be carried out, for example, according to the processes as described in Tetrahedron Letters (vol. 37, No. 17, pp. 2885-2886, 1996), or for example, by the following processes.

[1221] 1) Process of Producing Compound v-8 from Compound v-7

[1222] Compound v-8 can be produced by reacting compound v-7 with acetohydroxamic acid in a solvent in the presence of a base.

[1223] Amount of hydroxamic acid: 1 to 3 moles relative to 1 mole of compound v-7

[1224] Kind of base: potassium t-butoxide, sodium hydride, etc.

[1225] Amount of base: 1 to 3 moles relative to 1 mole of compound v-7

[1226] Solvent: N,N-dimethylformamide, dimethylsulfoxide, tetrahydrofuran, etc.

[1227] Reaction temperature: room temperature to 100° C.

[1228] Reaction time a moment to 100 hours

[1229] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1230] Reference Producing Process 3

[1231] This is the producing process according to the following scheme: 75

[1232] wherein R1, R2, R3, and R4 are as defined above; Y1 is oxygen, sulfur, or N—R142; and R142 is as defined above.

[1233] The reactions in the respective steps can be carried out, for example, by the following processes.

[1234] 1) Process of Producing Compound v-10 from Compound v-9

[1235] Compound v-10 can be produced by reacting compound v-9 with a nitrating agent in a solvent or without solvent.

[1236] Kind of nitrating agent: nitric acid etc.

[1237] Amount of nitrating agent: 1 to 15 moles relative to 1 mole of compound v-9

[1238] Solvent: acetic anhydride etc.

[1239] Reaction temperature: −10° C. to 50° C.

[1240] Reaction time: a moment to 100 hours

[1241] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1242] 2) Process of producing compound v-11 from compound v-10

[1243] Compound v-11 can be produced by reducing compound v-10 with iron powder in a solvent.

[1244] Amount of iron powder: 1 to 10 moles relative to 1 mole of compound v-10

[1245] Solvent: acetic acid, water, and mixtures thereof, etc.

[1246] Reaction temperature: 15° C. to 110° C.

[1247] Reaction time: a moment to 100 hours

[1248] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1249] Reference Producing Process 4

[1250] This is the producing process according to the following scheme: 76

[1251] wherein R226 is C1-C10 alkyl and M12 is fluorine or chlorine.

[1252] The reactions in the respective steps can be carried out, for example, according to the processes as described in Khim. Geterotsikl. Soedin (1990, Issue 5, pp. 597-600), Khim. Geterotsikl. Soedin (1989, Issue 5, pp. 704), or for example, by the following processes.

[1253] 1) Process of Producing Compound v-13 from Compound v-12

[1254] Compound v-13 can be produced by reacting compound v-12 with nitroenamine compound v-18 of the formula: 77

[1255] in a solvent and, if necessary, in the presence of an acid.

[1256] Amount of compound v-18: 1 to 3.0 moles relative to 1 mole of compound v-12

[1257] Kind of acid: acetic acid, p-toluenesulfonic acid, sulfuric acid, etc.

[1258] Amount of acid: a catalytic amount to a large excess amount relative to 1 mole of compound v-12

[1259] Solvent: aromatic hydrocarbons such as toluene and xylene; ethers such as tetrahydrofuran; organic acids such as acetic acid and propionic acid; amides such as N,N-dimethylformamide; and mixtures thereof; etc.

[1260] Reaction temperature: −10° C. to the reflux temperature of the solvent

[1261] Reaction time: a moment to 100 hours

[1262] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1263] 2) Process of Producing Compound v-14 from Compound v-13

[1264] Compound v-14 can be produced by reacting compound v-13 with an alkylcarbonylating agent in a solvent and, if necessary, in the presence of an acid and a base.

[1265] Kind of alkylcarbonylating agent: acetic anhydride, acetyl chloride, etc.

[1266] Amount of alkylcarbonylating agent: 1 to 2.0 moles relative to 1 mole of compound v-13

[1267] Kind of acid: acetic acid, p-toluenesulfonic acid, sulfuric acid, etc.

[1268] Amount of acid: a catalytic amount to a large excess amount relative to 1 mole of compound v-13

[1269] Kind of base: sodium hydroxide, potassium carbonate, triethylamine, etc.

[1270] Amount of base: a catalytic amount to a large excess amount relative to 1 mole of compound v-13

[1271] Solvent: aromatic hydrocarbons such as toluene and xylene; ethers such as tetrahydrofuran; organic acids such as acetic acid and propionic acid; inorganic acids such as sulfuric acid; amides such as N,N-dimethylformamide; and mixtures thereof; etc.

[1272] Reaction temperature: −10° C. to the reflux temperature of the solvent

[1273] Reaction time: a moment to 100 hours

[1274] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound- can be purified by a technique such as recrystallization or column chromatography.

[1275] 3) Process of Producing Compound v-15 from Compound v-14

[1276] Compound v-15 can be produced by reducing compound v-14 with iron powder in a solvent.

[1277] Amount of iron powder: 1 to 10 moles relative to 1 mole of compound v-14

[1278] Solvent: acetic acid, water, and mixtures thereof, etc.

[1279] Reaction temperature: 15° C. to 110° C.

[1280] Reaction time: a moment to 100 hours

[1281] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1282] Reference Producing Process 5

[1283] This is the producing process according to the following scheme: 78

[1284] wherein R1, R2, R3, R4, and A are as defined above; Y2 is nitrogen or C—R152; and R152 is as defined above.

[1285] The reaction can be carried out, for example, according to the processes as described in Synthesis (Issue 1, pp. 1-17, 1977), J. Med. Chem. (Vol. 39, pp. 570-581, 1996), or for example, by the following process.

[1286] 1) Process of Producing Compound x-3 from Compound x-5

[1287] Compound x-3 can be produced by reacting compound x-5 with an aminating agent in a solvent in the presence of a base.

[1288] Kind of base: inorganic bases such as potassium carbonate, sodium hydride, sodium hydroxide, and potassium hydroxide; etc.

[1289] Amount of base: 1 to 20 moles relative to 1 mole to compound x-75

[1290] Kind of aminating agent: hydroxylamine=O-sulfonic acid, chloramine, O-(2,4-dinitrophenyl)hydroxylamine, etc.

[1291] Amount of aminating agent: 0.9 to 5 moles relative to 1 mole of compound x-5

[1292] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; and mixtures thereof; etc.

[1293] Reaction temperature: −10° C. to the reflux temperature of the solvent

[1294] Reaction time: a moment to 48 hours

[1295] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1296] Compound x-5 used as the intermediate in the above reaction can be produced, for example, according to the processes as described in JP-A 7-508259, JP-A 7-508500, WO93/18008, and WO94/25446.

[1297] Reference Producing Process 6

[1298] This is the producing process according to the following scheme: 79

[1299] wherein R1, R2, R3, R4, and Y11 are as defined above.

[1300] The reaction can be carried out, for example, according to the process as described in Chem. Pharm. Bull 32(11), pp. 4260-4270 (1984), or for example, by the following scheme:

[1301] 1) Process of Producing Compound v-20 from Compound v-1

[1302] Compound v-20 can be produced by reacting compound v-1 with bromonitromethane in a solvent in the presence of a base.

[1303] Kind of base: inorganic bases such as potassium carbonate, sodium hydride, and sodium hydroxide; organic bases such as triethylamine; nitrogen-containing compounds such as pyridine; metal alcoholates such as sodium methylate and sodium ethylate; etc.

[1304] Amount of base: 1 to 5 moles relative to 1 mole of compound v-1

[1305] Amount of bromonitromethane: 0.9 to 3 moles realtive to 1 mole of compound v-1

[1306] Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ketones such as acetone; ethers such as tetrahydrofuran; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; and mixtures thereof; etc.

[1307] Reaction temperature: 0° C. to the reflux temperature of the solvent

[1308] Reaction time: a moment to 48 hours

[1309] After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

[1310] Reference Producing Process 7

[1311] This is the producing process according to the following scheme: 80

[1312] wherein R1, R2, R3, R4, R221, Y11, and Q are as defined above.

[1313] The reactions in the respective steps can be carried out according to the processes as described in Producing Processes 1 to 23.

[1314] The benzonitrile derivatives used in Reference Producing Processes 1 and 2 can be produced from the corresponding benzaldehyde derivatives or benzamide derivatives. (see Shin Jikken Kagaku Koza, edited by Nihon Kagaku Kai, Maruzen Kabushiki Kaisha, 14, pp. 1466-1474.)

[1315] Examples of the present compounds which can be prepared according to the above producing process are illustrated below; however, the present invention is not limited to these examples.

[1316] In the examples, Me indicates methyl; Et, ethyl; Pr, propyl; Bu, butyl; Pen, pentyl; Hex, hexyl; Hep, heptyl; Oct, octyl; i-, iso-; s-, sec-; c-, cyclo-; and groups not particularly indicated are in normal form.

[1317] Compounds of the general formulas: 81 82 83 84 85 86 87 88 89 90 91 92

[1318] wherein

[1319] A's are selected from nitrogen or CH;

[1320] Y1's are selected from oxygen or sulfur;

[1321] Y2's are selected from nitrogen or CH;

[1322] R2's are selected from hydrogen, fluorine, chlorine, bromine, iodine, CH2OH, CHO, COOH, CONH2, COC1, SO2Cl, COCH3, SH, OH, NH2, NO2, CN, CH3, CH2Br, CHB2, CBr3, CH2F, CHF2, CF3, O—Me, O-Et, O—Pr, O-i-Pr, O-Bu, O-i-Bu, O-s-Bu, O-Pen, O-c-Pen, O-Hex, O-c-Hex, O-Hep, O-Oct, OCH2CH2F, OCH2CH2Cl, OCH2CH2Br, OCH2CF3, OCH2OCH3, OCH2CH2OCH3, OCH2—CH2OCH2CH3, OCH2SCH3, OCH2CH2SCH3, OCH2CH2SCH2CH3, OCH2—CH═CH2, OCH(CH3)CH═CH2, OC(CH3)2CH═CH2, OCH2C(Cl)=CH2, OCH(CH3)C(Cl)=CH2, OCH2C(CH3)═CH2, OCH2C≡CH, OCH(CH3)C≡CH, OC(CH3)2C≡CH, OCH2-c-Pr, OCH2-c-Pen, OCH2-c-Hex, OCH2CN, OCH(CH3)CN, OCOMe, OCOEt, OCOPr, OCO-i-Pr, OCOCF3, OCOCF2H, OCH2COOH, OCH2COOMe, OCH2COOEt, OCH2COOPr, OCH2COO-i-Pr, OCH2COOBu, OCH2COO-s-Bu, OCH2COOPen, OCH2COOHex, OCH2—COOHep, OCH2COO-c-Pen, OCH2COO-c-Hex, OCH2COOCH2CH═CH2, OCH2COOCH2C≡CH, OCH2COOPh, OCH2COOCH2Ph, OCH2C(═NOMe)—COOMe, OCH2C(═NOMe)COOEt, OCH2C(═NOMe)COOPr, OCH2COOCH2—COOH, OCH2COOCH2COOMe, OCH2COOCH2COOEt, OCH2COOCH2—COOPr, OCH2COOCH2COO-i-Pr, OCH2COOCH2COOBu, OCH2COOCH2—COO-c-Pen, OCH2COOCH2COO-c-Hex, OCH2COOCH2COOCH2CH═CH2, OCH2COOCH2COOCH2C≡CH, OCH2COOCH(CH3)COOH, OCH2COO—CH(CH3)COOMe, OCH2COOCH(CH3)COOEt, OCH2COOCH(CH3)COOPr, OCH2COOCH(CH3)COO-i-Pr, OCH2COOCH(CH3)COOBu, OCH2COO—CH(CH3)COO-c-Pen, OCH2COOCH(CH3)COO-c-Hex, OCH2COOCH(CH3)—COOCH2CH═CH2, OCH2COOCH(CH3)COOCH2C≡CH, OCH2COOC(CH3)2—COOH, OCH2COOC(CH3)2COOMe, OCH2COOC(CH3)2COOEt, OCH2COO—C(CH3)2COOPr, OCH2COOC(CH3)2COO-i-Pr, OCH2COOC(CH3)2COOBu, OCH2COOC(CH3)2COO-c-Pen, OCH2COOC(CH3)2COO-c-Hex, OCH2COO—C(CH3)2COOCH2CH═CH2, OCH2COOC(CH3)2COOCH2C≡CH, OCH(CH3)—COOH, OCH(CH3)COOMe, OCH(CH3)COOEt, OCH(CH3)COOPr, OCH(CH3)COO-i-Pr, OCH(CH3)COOBu, OCH(CH3)COO-s-Bu, OCH(CH3)—COOPen, OCH(CH3)COOHex, OCH(CH3)COOHep, OCH(CH3)COO-c-Pen, OCH(CH3)COO-c-Hex, OCH(CH3)COOCH2CH═CH2, OCH(CH3)COOCH2 C≡CH, OCH(CH3)COOPh, OCH(CH3)COOCl2Ph, OCH(CH3)C(═NOMe)—COOMe, OCH(CH3)C(═NOMe)COOEt, OCH(CH3)C(═NOMe)COOPr, OCH(CH3)COOCH2COOH, OCH(CH3)COOCH2COOMe, OCH(CH3)COOCH2—COOEt, OCH(CH3)COOCH2COOPr, OCH(CH3)COOCH2COO-i-Pr, OCH(CH3)COOCH2COOBu, OCH(CH3)COOCH2COO-c-Pen, OCH(CH3)—COOCH2COO-c-Hex, OCH(CH3)COOCH2COOCH2CH═CH2, OCH(CH3)COO—CH2COOCH2C≡CH, OCH(CH3)COOCH(CH3)COOH, OCH(CH3)COO—CH(CH3)COOMe, OCH(CH3)COOCH(CH)COOEt, OCH(CH3)COOCH(CH3)—COOPr, OCH(CH3)COOCH(CH3)COO-i-Pr, OCH(CH3)COOCH(CH3)COOBu, OCH(CH3)COOCH(CH3)COO-c-Pen, OCH(CH3)COOCH(CH3)COO-c-Hex, OCH(CH3)COOCH(CH3)COOCH2CH═CH2, OCH(CH3)COOCH(CH3)COOCH2C≡CH, OCH(CH,)COOC(CH3)2COOH, OCH(CH3)COOC(CH3)2COOMe, OCH(CH3)COOC(CH3)2COOEt, OCH(CH3)COOC(CH3)2COOPr, OCH(CH3)—COOC(CH3)2COO-i-Pr, OCH(CH3)COOC(CH3)2COOBu, OCH(CH3)COO—C(CH3)2COO-c-Pen, OCH(CH3)COOC(CH3)2COO-c-Hex, OCH(CH3)COO—C(CH3)2COOCH2CH═CH2, OCH(CH3)COOC(CH3)2COOCH2C≡CH, OCH2—CON(Me)2, OCH2CON(Et)2, OCH(CH3)CON(Me)2, OCH(CH3)CON(Et)2, S—Me, S-Et, S-Pr, S-i-Pr, S-Bu, S-1-Bu, S-s-Bu, S-Pen, S-c-Pen, S-Hex, S-c-Hex, S-Hep, S-Oct, SCH2CH2F, SCH2CH2Cl, SCH2CH2Br, SCH2CF3, SCH2OCH3, SCH2CH2OCH3, SCH2CH2OCH2CH3, SCH2SCH3, SCH2CH2SCH3, SCH2CH2—SCH2CH3, SCH2CH═CH2, SCH(CH3)CH═CH2, SC(CH3)2CH═CH2, SCH2—C(Cl)═CH2, SCH(CH3)C(Cl)═CH2, SCH2C(CH3)═CH2, SCH2C≡CH, SCH(CH3)C≡CH, SC(CH3)2C≡CH, SCH2-c-Pr, SCH2-c-Pen, SCH2-c-Hex, SCH2CN, SCH(CH3)CN, SCOMe, SCOEt, SCOPr, SCO-i-Pr, SCOCF3, SCOCF2H, SCH2COOH, SCH2COOMe, SCH2COOEt, SCH2COOPr, SCH2—COO-i-Pr, SCH2COOBu, SCH2COO-s-Bu, SCH2COOPen, SCH2COOHex, SCH2COOHep, SCH2COO-c-Pen, SCH2COO-c-Hex, SCH2COOCH2CH═CH2, SCH2COOCH2C—CH, SCH2COOPh, SCH2COOCH2Ph, SCH2COOCH2COOH, SCH2COOCH2COOMe, SCH2COOCH2COOEt, SCH2COOCH2COOPr, SCH2—COOCH2COO-i-Pr, SCH2COOCH2COOBu, SCH2COOCH2COO-c-Pen, SCH2—COOCH2COO-c-Hex, SCH2COOCH2COOCH2CH═CH2, SCH2COOCH2COO—CH2C═CH, SCH2COOCH(CH3)COOH, SCH2COOCH(CH3)COOMe, SCH2—COOCH(CH3)COOEt, SCH2COOCH(CH)COOPr, SCH2COOCH(CH3) COO-i-Pr, SCH2COOCH(CH3)COOBu, SCH2COOCH(CH3)COO-c-Pen, SCH2COO—CH(CH3)COO-c-Hex, SCH2COOCH(CH3)COOCH2CH═CH2, SCH2COO—CH(CH3)COOCH2C≡CH, SCH2COOC(CH3)2COOH, SCH2COOC(CH3)2—COOMe, SCH2COOC(CH3)2COOEt, SCH2COOC(CH3)2COOPr, SCH2COO—C(CH3)2COO-i-Pr, SCH2COOC(CH3)2COOBu, SCH2COO C(CH3)2COO-c-Pen, SCH2COOC(CH3)2COO-c-Hex, SCH2COOC(CH3)2COOCH2CH═CH2, SCH2—COOC(CH3)2COOCH2C CH, SCH(CH3)COOH, SCH(CH3)COOMe, SCH(CH3)COOEt, SCH(CH3)COOPr, SCH(CH3)COO-i-Pr, SCH(CH3)COOBu, SCH(CH3)COO-s-Bu, SCH(CH3)COOPen, SCH(CH3)COOHex, SCH(CH3)—COOHep, SCH(CH3)COO-c-Pen, SCH(CH3)COO-c-Hex, SCH(CH3)COO—CH2CH═CH2, SCH(CH3)COOCH2C═CH, SCH(CH3)COOPh, SCH(CH3)—COOCH2Ph, SCH(CH3)COOCH2COOH, SCH(CH3)COOCH2COOMe, SCH(CH3)COOCH2COOEt, SCH(CH3)COOCH2COOPr, SCH(CH3)COOCH2—COO-i-Pr, SCH(CH3)COOCH2COOBu, SCH(CH3)COOCH2COO-c-Pen, SCH(CH3)COOCH2COO-c-Hex, SCH(CH3)COOCH2COOCH2CH═CH2, SCH(CH3)COOCH2COOCH2C≡CH, SCH(CH3)COOCH(CH3)COOH, SCH(CH3)COOCH(CH3)COOMe, SCH(CH3)COOCH(CH3)COOEt, SCH(CH3)COOCH(CH3)COOPr, SCH(CH3)COOCH(CH3)COO-i-Pr, SCH(CH3)COOCH(CH3)COOBu, SCH(CH3)COOCH(CH3)COO-c-Pen, SCH(CH3)COOCH(CH3)COO-c-Hex, SCH(CH3)COOCH(CH3)COOCH2—CH═CH2, SCH(CH3)COOCH(CH3)COOCH2C≡CH, SCH(CH3)COOC(CH3)2—COOH, SCH(CH3)COOC(CH3)2COOMe, SCH(CH3)COOC(CH3)2COOEt, SCH(CH3)COOC(CH3)2COOPr, SCH(CH3)COOC(CH3)2COO-i-Pr, SCH(CH3)—COOC(CH3)2COOBu, SCH(CH3)COOC(CH3)2COO-c-Pen, SCH(CH3)COO—C(CH3)2COO-c-Hex, SCH(CH3)COOC(CH3)2COOCH2CH═CH2, SCH(CH3)—COOC(CH3)2COOCH2C≡CH, SCH2CON(Me)2, SCH2CON(Et)2, SCH(CH3)—CON(Me)2, SCH(CH3)CON(Et)2, NH-Me, NH-Et, NH-Pr, NH-i-Pr, NH-Bu, NH-i-Bu, NH-s-Bu, NH-Pen, NH-c-Pen, NH-Hex, NH-c-Hex, NH-Hep, NH-Oct, NHCH2CH═CH2, NHCH(CH3)CH═CH2, NHC(CH3)2CH═CH2, NHCH2—C(Cl)═CH2, NHCH(CH3)C(Cl)═CH2, NHCH2C(CH3)═CH2, NHCH2C═CH, NHCH(CH3)C≡CH, NHC(CH3)2C≡CH, NHCH2-c-Pr, NHCH2-c-Pen, NH—CH2-c-Hex, NHCH2CN, NHCH(CH3)CN, NHCOMe, NHCOEt, NHCOPr, NHCO-i-Pr, NHCOCF3, NHCOCF2H, NHCOOMe, NHCOOEt, NHCOOPr, NHCOO-i-Pr, NHSO2Me, NHSO2Et, NHSO2Pr, NHSO2-i-Pr, NHSO2CH2Cl, NHSO2CF3, NHCH2COOH, NHCH2COOMe, NHCH2COOEt, NHCH2COOPr, NHCH2COO-i-Pr, NHCH2COOBu, NHCH2COO-s-Bu, NHCH2COOPen, NHCH2COOHex, NHCH2COOHep, NHCH2COO-c-Pen, NHCH2COO-c-Hex, NHCH2COOCH2CH═CH2, NHCH2COOCH2C═CH, NHCH2COOPh, NHCH2—COOCH2Ph, NHCH2COOCH2COOH, NHCH2COOCH2COOMe, NHCH2—COOCH2COOEt, NHCH2COOCH2COOPr, NHCH2COOCH2COO-i-Pr, NH—CH2COOCH2COOBu, NHCH2COOCH2COO-c-Pen, NHCH2COOCH2COO-c-Hex, NHCH2COOCH2COOCH2CH═CH2, NHCH2COOCH2COOCH2C≡CH, NHCH2COOCH(CH3)COOH, NHCH2COOCH(CH3)COOMe, NHCH2COO—CH(CH3)COOEt, NHCH2COOCH(CH3)COOPr, NHCH2COOCH(CH3) COO-i-Pr, NHCH2COOCH(CH3)COOBu, NHCH2COOCH(CH3)COO-c-Pen, NHCH2—COOCH(CH3)COO-c-Hex, NHCH2COOCH(CH3)COOCH2CH═CH2, NHCH2—COOCH(CH3)COOCH2C≡CH, NHCH2COOC(CH3)2COOH, NHCH2COO—C(CH3)2COOMe, NHCH2COOC(CH3)2COOEt, NHCH2COOC(CH3)2COOPr, NHCH2COOC(CH3)2COO-i-Pr, NHCH2COOC(CH3)2COOBu, NHCH2COO—C(CH3)2COO-c-Pen, NHCH2COOC(CH3)2COO-c-Hex, NHCH2COOC(CH3)2—COOCH2CH═CH2, NHCH2COOC(CH3)2COOCH2C≡CH, NHCH(CH3)COOH, NHCH(CH)COOMe, NHCH(CH3)COOEt, NHCH(CH3)COOPr, NHCH(CH3)—COO-i-Pr, NHCH(CH3)COOBu, NHCH(CH3)COO-s-Bu, NHCH(CH3)COO-Pen, NHCH(CH3)COOHex, NHCH(CH3)COOHep, NHCH(CH3)COO-c-Pen, NHCH(CH3)COO-c-Hex, NHCH(CH)COOCH2CH═CH2, NHCH(CH3)COO—CH2C≡CH, NHCH(CH3)COOPh, NHCH(CH3)COOCH2Ph, NHCH(CH3)—COOCH2COOH, NHCH(CH3)COOCH2COOMe, NHCH(CH3)COOCH2COOEt, NHCH(CH3)COOCH2COOPr, NHCH(CH3)COOCH2COO-i-Pr, NHCH(CH3)—COOCH2COOBu, NHCH(CH3)COOCH2COO-c-Pen, NHCH(CH3)COOCH2—COO-c-Hex, NHCH(CH3)COOCH2COOCH2CH═CH2, NHCH(CH3)COOCH2—COOCH2C≡CH, NHCH(CH3)COOCH(CH3)COOH, NHCH(CH3)COO—CH(CH3)COOMe, NHCH(CH3)COOCH(CH3)COOEt, NHCH(CH3)COO—CH(CH3)COOPr, NHCH(CH3)COOCH(CH3)COO-i-Pr, NHCH(CH3)COO—CH(CH3)COOBu, NHCH(CH3)COOCH(CH3)COO-c-Pen, NHCH(CH3)COO—CH(CH3)COO-c-Hex, NHCH(CH3)COOCH(CH3)COOCH2CH═CH2, NH—CH(CH3)COOCH(CH3)COOCH2C≡CH, NHCH(CH3)COOC(CH3)2COOH, NHCH(CH3)COOC(CH3)2COOMe, NHCH(CH3)COOC(CH3)2COOEt, NH—CH(CH3)COOC(CH3)2COOPr, NHCH(CH3)COOC(CH3)2COO-i-Pr, NH—CH(CH3)COOC(CH3)2COOBu, NHCH(CH3)COOC(CH3)2COO-c-Pen, NH—CH(CH3)COOC(CH3)2COO-c-Hex, NHCH(CH3)COOC(CH3)2COOCH2—CH═CH2, NHCH(CH3)COOC(CH)2COOCH2C≡CH, NHCH2CON(Me)2, NH—CH2CON(Et)2, NHCH(CH3)CON(Me)2, NHCH(CH3)CON(Et)2, COOH, COO-Me, COOEt, COOPr, COO-i-Pr, COOBu, COO-s-Bu, COOPen, COOHex, COOCH2Ph, COO-c-Pen, COO-c-Hex, COOCH2COOH, COOCH2COOMe, COOCH2COOEt, COOCH2COOPr, COOCH2COO-i-Pr, COOCH2COOBu, COOCH2COO-c-Pen, COOCH2COO-c-Hex, COOCH2COOCH2CH≡CH2, COO—CH2COOCH2C≡CH, COOCH(CH3)COOH, COOCH(CH3)COOMe, COO—CH(CH3)COOEt, COOCH(CH3)COOPr, COOCH(CH3)COO-i-Pr, COO—CH(CH3)COOBu, COOCH(CH3)COO-c-Pen, COOCH(CH3)COO-c-Hex, COO—CH(CH3)COOCH2CH═CH2, COOCH(CH3)COOCH2C≡CH, COOC(CH3)2—COOH, COOC(CH3)2COOMe, COOC(CH3)2COOEt, COOC(CH3)2COOPr, COOC(CH3)2COO-i-Pr, COOC(CH3)2COOBu, COOC(CH3)2COO-c-Pen, COO—C(CH3)2COO-c-Hex, COOC(CH3)2COOCH2CH═CH2, COOC(CH3)2COOCH2 C≡CH, CON(Me)2, CON(Et)2, CON(Me)2, CON(Et)2, CH2CH2COOH, CH2—CH2COOMe, CH2CH2COOEt, CH2CH2COOPr, CH2CH2COO-i-Pr, CH2CH2—COOBu, CH2CH(Cl)COOH, CH2CH(Cl)COOMe, CH2CH(Cl)COOEt, CH2—CH(Cl)COOPr, CH2CH(Cl)COO-i-Pr, CH2CH(Cl)COOBu, CH═CHCOOH, CH═CHCOOMe, CH═CHCOOEt, CH═CHCOOPr, CH═CHCOO-i-Pr, CH═CHCOOBu, CH═C(Cl)COOH, CH═C(Cl)COOMe, CH═C(Cl)COOEt, CH═C(Cl)COOPr, CH═C(Cl)COO-i-Pr, CH═C(Cl)COOBu, C(Me)═CHCOOH, C(Me)═CHCOOMe, C(Me)═CHCOOEt, C(Me)═CHCOOPr, C(Me)═CHCOO-i-Pr, C(Me)═CHCOOBu, CH═C(Me)COOH, CH═C(Me)COOMe, CH═C(Me)—COOEt, CH═C(Me)COOPr, CH═C(Me)COO-i-Pr, CH═C(Me)COOBu, CH═N—OH, CH═NOMe, CH═NOEt, CH═NOPr, CH═NO-i-Pr, CH═NOBu, C(Me)═N—OH, C(Me)—NOMe, C(Me)=NEt, C(Me)=NOPr, C(Me)=NO-i-Pr, C(Me)=N—OBu, CH═NOCH2COOMe, CH═NOCH2COOEt, CH═NOCH2COOPr, CH═N—OCH2COO-i-Pr, CH═NOCH2COOBu, C(Me)═NOCH2COOMe, C(Me)═NO—CH2COOEt, C(Me)=NOCH2COOPr, C(Me)=NOCH2COO-i-Pr, or (Me)═NO CH2COOBu;

[1323] R3's are selected from hydrogen, fluorine, chlorine, bromine, iodine, NO2, CN, O-Me, O-Et, O-Pr, O-i-Pr, O-Bu, O-1-Bu, O-s-Bu, O-Pen, O-c-Pen, O-Hex, O-c-Hex, O-Hep, O-Oct, OCH2COOMe, OCH2COOEt, OCH2COOPr, OCH2COO-i-Pr, OCH2COOBu, OCH2COO-s-Bu, OCH2COOPen, OCH2CO—OHex, OCH2COOHep, OCH2C(═NOMe)COOMe, OCH2C(═NOMe)COOEt, OCH2C(═NOMe)COOPr, OCH(CH3)COOMe, OCH(CH3)COOEt, OCH(CH3)—COOPr, OCH(CH3)COO-i-Pr, OCH(CH8)COOBu, OCH(CH3)COO-s-Bu, OCH(CH3)COOPen, OCH(CH3)COOHex, OCH(CH3)COOHep, OCH(CH3)—C(═NOMe)COOMe, OCH(CH3)C(═NOMe)COOEt, or OCH(CH3)C(═NOMe)—COOPr; and

[1324] R4's are selected from hydrogen, fluorine, chlorine, bromine, iodine, NO2, or CN.

EXAMPLES

[1325] The present invention will be further illustrated by the following Production Examples, Formulation Examples, and Test Examples; however, the present invention is not limited to these Examples. The numbers of the present compounds are those as shown in Tables 1 to 54.

Production Example 1

[1326] 93

[1327] To a suspension of 60.0 g of potassium carbonate in 300 ml of acetone was added 25 g of compound 1a and then added 35.7 g of ethyl bromoacetate, and the mixture was heated and stirred at the reflux temperature of acetone for 1 hour. The reaction mixture was then cooled to room temperature and filtered to remove insoluble matter. The filtrate was concentrated to give 45.8 g of compound 1b as a crude product

[1328] To a solution of 45.8 g of this crude product of compound 1b in 300 ml of N,N-dimethylformamide was added 30.0 g of potassium carbonate, and the mixture was heated and stirred at a temperature of 100° C. to 110° C. for 5 hours. The reaction mixture was then cooled to room temperature and poured into water, which was extracted with t-butyl methyl ether. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated to give 36.5 g of compound 1c as crystals.

[1329] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 1.44 (3H, t, J=7.09 Hz), 4.44 (2H, q, J=7.07 Hz), 4.65-5.38 (2H, br), 7.21-7.27 (1H, m), 7.44-7.57 (3H, m)

[1330] To a solution of 10.2 g of compound 1c in 50 ml of tetrahydrofuran was added 6.5 g of ethyl chloroformate and 7.3 g of N,N-diethylaniline, and the mixture was heated and stirred at the reflux temperature of tetrahydrofuran for 3 hours. The reaction mixture was then cooled to room temperature and poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated to give 13.05 g of compound 1d.

[1331] m.p.: 90.6° C.

[1332] To a suspension of 2.4 g of sodium hydride in 50 ml of N,N-dimethylformamide was added 11.0 g of ethyl 4,4,4-trifluoro-3-aminochrotonate below 10° C., and the mixture was stirred for 30 minutes. The reaction mixture was then warmed to room temperature, to which a solution of 13.0 g of compound 1d in 20 ml of N,N-dimethylformamide was added, and the reaction mixture was then warmed to 100° C. to 110° C., at which temperature the mixture was kept and stirred for 2.5 hours. The reaction mixture was then cooled to room temperature, to which 10.0 g of methyl iodide was added, and the mixture was stirred at room temperature overnight. The reaction mixture was then poured into water, which was extracted with t-butyl methyl ether. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=4:1) to give 4.56 g of compound 1e.

[1333] m.p.: 107.2° C.

[1334] First, 1.0 g of compound 1e was added to 5 ml of 85% sulfuric acid, and the mixture was warmed to 110° C., heated and stirred for 5 minutes. The reaction mixture was then poured into water, and the deposited crystals were collected by filtration and dried to give 0.81 g of compound 1f.

[1335] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 3.59-3.60 (3H, m), 6.41 (1H, s), 7.26-7.67 (4H, m)

[1336] First, 0.7 g of compound 1f and 0.05 g of copper powder were added to 3 ml of quinoline, and the mixture was warmed to 150° C., at which temperature the mixture was kept and stirred for 1 hour. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane ethyl acetate=5:1) to give 0.43 g of compound 1g (the present compound 1-1).

[1337] 1H-NMR (250 MHz, CDCl3, TMS, 6 &mgr;m)): 3.51 (3H, m), 6.34 (1H, s), 7.21-7.54 (4H, m), 7.81 (1H, s)

Production Example 2

[1338] 94 95

[1339] To 200 ml of ethanol were added 25 g of compound 2a and 10.9 g of hydroxylamine hydrochloride, and the mixture was stirred at room temperature overnight., The reaction mixture was then poured into water, and the deposited crystals were collected by filtration and dried to give 26.06 g of compound 2b.

[1340] To a solution of 26.0 g of compound 2b in 100 ml of chloroform was added 22.4 g of 1,1′-carbonyldiimidazole under ice cooling, and the mixture was stirred at room temperature for 30 minutes, then heated and stirred at the reflux temperature of chloroform for 1 hour. The reaction mixture was then concentrated, and diluted hydrochloric acid was added to the residue, which was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated to give 15.88 g of compound 2c.

[1341] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 7.46 (1H, d, J=2.45 Hz), 7.57 (1H, d, J=2.45 Hz).

[1342] To a suspension of 16.5 g of potassium carbonate in 80 ml of acetone was added 15 g of compound 2c and then added 14.6 g of ethyl bromoacetate, and the mixture was heated and stirred at the reflux temperature of acetone for 4 hours. The reaction mixture was then cooled to room temperature and filtered to remove insoluble matter, and the filtrate was then concentrated to give compound 2d as a crude product.

[1343] To a solution of this crude product of compound 2d in 150 ml of N,N-dimethylformamide was added 50.0 g of potassium carbonate, and the mixture was heated and stirred at a temperature of 90° C. to 100° C. for 30 minutes. The reaction mixture was then cooled to room temperature and poured into water, and the deposited crystals were collected by filtration. The crystals were washed with water and dried to give 21.49 g of compound 2e.

[1344] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 1.44 (3H, t, J=7.07 Hz), 4.45 (2H, q, J=7.07 Hz), 4.82-5.13 (2H, br), 7.44-7.45 (2H, m)

[1345] To 60 ml of toluene were added 4.0 g of compound 2e, 2.8 g of trichloromethyl chloroformate, and 1 g of activated carbon powder), and the mixture was heated and stirred at the reflux temperature of toluene for 1 hour. The reaction mixture was then filtered, and the filtrate was concentrated to give 13.0 g of compound 2f as a crude product.

[1346] In a suspension of 0.64 g of sodium hydride in 20 ml of N,N-dimethylformamide was added 3.0 g of ethyl 4,4,4-trifluoro-3-aminichrotonate below 10° C., and the mixture was stirred for 30 minutes. To the reaction mixture was added dropwise at −30° C. a solution of 13.0 g of this crude product of compound 2f in 30 ml of tetrahydrofuran. After completion of the dropwise addition, the reaction mixture was warmed to room temperature and stirred at room temperature for 2 hours. To the reaction mixture was then added 3.0 g of methyl iodide, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, then and concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate 4:1) to give 4.51 g of compound 2g.

[1347] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 1.33 (3H, t, J=7.06 Hz), 3.59 (3H, m), 4.39 (2H, q, J=6.93 Hz), 6.39 (1H, s), 7.36 (1H, d, J=2.65 Hz), 7.51 (1H, d, J=2.65 Hz)

[1348] First, 4.5 g of compound 2g was added to 20 ml of 85% sulfuric acid, and the mixture was heated to 110° C., at which temperature the mixture was kept and stirred for 30 minutes. The reaction mixture was then poured into water, and the deposited crystals were collected by filtration and dried to give 3.57 g of compound 2h.

[1349] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)) 3.59-3.60 (3H, m), 6.40 (1H, s), 7.38 (1H, d, J=1.77 Hz), 7.54 (1H, d, J=1.77 Hz)

[1350] To 10 ml of quinoline were added 3.0 g of compound 2h and 0.07 g of copper powder, and the mixture was heated to 120° C. to 150° C., at which temperature the mixture was kept and stirred for 30 minutes. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 1.62 g of compound 2i (the present compound 1-2).

[1351] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 3.59-3.60 (3H, m), 6.40 (1H, s), 7.24 (1H, d, J=1.89), 7.37 (1H, d, J=1.89), 7.93 (1H, s)

Production Example 3

[1352] 96

[1353] To a solution of 9.77 g of acetohydroxamic acid in 150 ml of N,N-dimethylformamide was added 14.6 g of potassium t-butoxide at room temperature, and the mixture was stirred at room temperature for 30 minutes. To the reaction mixture was added 10.5 g of compound 3a at room temperature, and the mixture was left undisturbed at room temperature for 3 days. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with n-hexane to give 6.95 g of compound 3b.

[1354] To 2 ml of propionic acid were added 500 mg of compound 3b and 567 mg of 3,4,5,6-tetrahydrophthalic anhydride, and the mixture was heated and stirred at the reflux temperature of propionic acid for 24 hours. The reaction mixture was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=5:1) to give 200 mg of compound 3c (the present compound 2-4).

[1355] 1H-NMR (250 MHz, CDCl3, TMS, 6 &mgr;m)): 1.84-1.89 (4H, m), 2.48-2.52 (4H, m), 7.31-7.40 (1H, m), 7.55-7.75 (3H, m)

Production Example 4

[1356] 97

[1357] To a solution of 10.4 g of ethyl thioglycolate in 20 ml of N,N-dimethylformamide were added 12.4 g of potassium carbonate and 20 ml of N,N-dimethylformamide, and the mixture was warmed to 40° C. To the reaction mixture was added 10.0 g of compound 4a, and the mixture was warmed to 85° C., at which temperature the mixture was kept and stirred for 2 hours. The reaction mixture was left undisturbed at room temperature overnight. To the reaction mixture were then added 33.7 g of potassium carbonate and 30 ml of N,N-dimethylformamide, and the mixture was heated and stirred at 100° C. to 110° C. for 4 hours. The reaction solution was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=4:1) to give 14.44 g of compound 4b.

[1358] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 1.39 (3H, t, J=7.09 Hz), 4.36 (2H, q, J=7.11 Hz), 5.90 (2H, bs), 7.34-7.74 (4H, m)

[1359] To a solution of 4.0 g of compound 4b in 50 ml of toluene was added 3.58 g of trichloromethyl chloroformate, and the mixture was heated and stirred at the reflux temperature of toluene for 1 hour. The reaction mixture was concentrated to give compound 4c as a crude product.

[1360] To a suspension of 0.87 g of sodium hydride in 15 ml of N,N-dimethylformamide was added 4.0 g of ethyl 4,4,4-trifluoro-3-aminochrotonate below 10° C., and the mixture was stirred for 30 minutes. To the reaction was then added dropwise at −30° C. a solution of this crude product of compound 4c in the whole amount dissolved in 50 ml of tetrahydrofuran. After completion of the dropwise addition, the mixture was warmed to room temperature and left undisturbed overnight. To the reaction mixture was then added 3.85 g of methyl iodide, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=4:1) to give 2.36 g of compound 4b as crystals.

[1361] m.p.: 112.6° C.

[1362] To 15 ml of 85% sulfuric acid was added 2.3 g of compound 4d, and the mixture was warmed to 110° C., at which temperature the mixture was kept and stirred for 15 minutes. The reaction mixture was then poured into water, and the precipitated crystals were collected by filtration and dried to give 1.61 g of compound 4e.

[1363] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 3.58 (3H, m), 6.42 (1H, s), 7.41-7.91 (4H, m)

[1364] To 12 ml of quinoline were added 1.5 g of compound 4e and 0.06 g of copper powder, and the mixture was warmed to 120° C. to 140° C., at which temperature the mixture was kept and stirred for 30 minutes. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=4:1) to give 1.07 g of compound 4f (the present compound 1-3).

[1365] m.p.: 156.8° C.

Production Example 5

[1366] 98

[1367] According to the process as described above in Production Example 2, compound 5a (the present compound 1-6) was produced from 2-hydroxy-5-nitrobenzaldehyde.

[1368] m.p.: 231.9° C. (decomposition)

[1369] To a mixed solvent of 40 ml of acetic acid and 20 ml of water was added 4.5 g of iron powder, to which suspension 4.5 g of compound 5a was added, and the mixture was heated and stirred at the reflux temperature of the solvent for 20 minutes. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, and then concentrated to give 2.64 g of compound 5b (the present compound 1-7).

[1370] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.25-3.82 (2H, br), 3.58 (3H, m), 6.39 (1H, s), 6.55 (1H, d, J=2.30 Hz), 6.71 (1H, dd, J=8.76 Hz, 2.30 Hz), 7.32 (1H, d, J=8.76 Hz), 7.73 (1H, s)

[1371] To a solution of 0.8 g of compound 5b dissolved in 6 ml of pyridine was added 0.3 g of methanesulfonyl chloride at room temperature, and the mixture was stirred for 2 hours. The reaction mixture was poured into water, which was extracted with ethyl acetate. The organic layer was washed with water, with aqueous hydrochloric acid solution, and then with water, dried over anhydrous magnesium sulfate, and then concentrated. The deposited crystals were washed with t-butyl methyl ether to give 0.55 g of compound 5c (the present compound 1-10).

[1372] m.p.: 105.3° C.

Production Example 6

[1373] 99

[1374] To 6 ml of methyl iodide was added 0.6 g of compound 5b, and the mixture was heated and stirred at the reflux temperature of methyl iodide for 4 hours. The reaction mixture was concentrated, and the residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) to give 0.14 g of compound 6a (the present compound 1-8) and 0.065 g of compound 6b (the present compound 1-9).

[1375] Compound 6a

[1376] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 2.82 (3H, s), 3.57-3.58 (3H, m), 6.37-6.67 (3H, m), 7.33 (1H, d, J=8.85 Hz), 7.71 (1H, s)

[1377] Compound 6b

[1378] m.p.: 166.1C (decomposition)

Production Example 7

[1379] 100

[1380] To 10 ml of acetonitrile were added 0.53 g of copper (I) chloride and 0.57 g of isobutyl nitrite, to which 3 ml of ethyl acrylate was added under ice cooling, and the mixture was stirred for 10 minutes. A solution of 1.0 g of compound 5b dissolved in 5 ml of acetonitrile was then added to the reaction mixture under ice cooling. The mixture obtained was stirred for 2 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=3:1) to give 0.64 g of compound 7a (the present compound 1-407).

[1381] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 1.18 (3H, t, J=7.12 Hz), 3.18-3.48 (2H, m), 3.56-3.57 (3H, m), 4.10-4.20 (2H, m), 4.41 (1H, t, J=7.43 Hz), 6.39 (1H, s), 7.19-7.49 (3H, m), 7.82 (1H, s)

Production Example 8

[1382] 101

[1383] According to the process as described above in Production Example 2, compound 8a (the present compound 1-5) was produced from 2-hydroxy-5-methoxybenzaldehyde.

[1384] m.p.: 135.0° C.

[1385] To a solution of 0.64 g of compound 8a dissolved in 4 ml of chloroform was added 0.5 g of iodotrimethylsilane, and the mixture was kept and stirred at 40° C. to 50° C. for 10.5 hours. The mixture was then left undisturbed at room temperature for a half day, to which 0.5 g of iodotrimethylsilane was further added, and the mixture was further kept and stirred at 40° C. to 50° C. for 10.5 hours. The reaction mixture was then poured into ice water, which was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) to give 0.37 g of compound 8b (the present compound 1-78).

[1386] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 3.58-3.59 (3H, m), 5.09 (1H, bs) 6.39 (1H, s), 6.68 (1H, d, J=2.32 Hz), 6.82 (1H, dd, J=8.83 Hz, 2.32 Hz), 7.37 (1H, d, J=8.85 Hz), 7.79 (1H, s)

[1387] To a suspension of 0.05 g of sodium hydride in 1 ml of N,N-dimethylformamide was added a solution of 0.35 g of compound 8b in 2 ml of N,N-dimethylformamide under ice cooling, and the mixture was stirred for 5 minutes. Then, 0.23 g of ethyl bromoacetate was added under ice cooling, and the mixture was stirred for 0.5 hour. The reaction mixture was poured into water, which was extracted with ethyl acetate. The organic layer was washed with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) to give 0.34 g of compound 8c (the present compound 1-127).

[1388] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 1.21 (3H, t, J=7.06 Hz), 1.60 (3H, d, J=6.82 Hz), 3.58-3.59 (3H, m), 4.10-4.23 (2H, m), 4.73 (1H, q, J=6.82 Hz), 6.38 (1H, s), 6.74 (1H, d, J=2.52 Hz), 6.97 (1H, dd, J=9.21 Hz, 2.80 Hz), 7.43 (1H, d, J=9.29 Hz), 7.80 (1H, s)

Production Example 9

[1389] 102

[1390] In a solution of 1.0 g of compound 5b dissolved in 10 ml of acetic acid was added 0.045 g of acetic anhydride, and the mixture was stirred at room temperature for 3 hours. A mixed solution of hexane:ethyl acetate=1:1 was then added, and the deposited crystals were collected by filtration and dried to give 1.16 g of compound 9a (the present compound 1-24).

[1391] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 2.10 (3H, s), 3.59 (3H, s), 6.39 (1H, s), 7.12 (1H, dd, J=8.80 Hz, 2.10 Hz), 7.29 (1H, bs), 7.44 (1H, d, J=8.82 Hz), 7.77 (1H, d, J=1.88 Hz), 7.81 (1H, s)

[1392] In a solution of 1.0 g of compound 9a dissolved in 10 ml of dimethylformamide was added 0.11 g of sodium hydride at room temperature, and the mixture was stirred for 10 minutes. Then, 0.43 g of methyl iodide was added at room temperature, and the mixture was left undisturbed for 3 days. The reaction mixture was then poured into water, which was extracted with t-butyl methyl ether. The organic layer was washed with water and then with diluted hydrochloric acid, and dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 0.36 g of compound 9b (the present compound 1-28).

[1393] m.p.: 207.2° C.

Production Example 10

[1394] 103

[1395] According to the process as described above in Production Example 2, compound 10a (the present compound 1-75) was produced from 2-hydroxy-5-bromobenzaldehyde.

[1396] m.p.: 130.0° C.

[1397] To a solution of 1.85 g of compound 10a in 10 ml of N-methylpyrrolidone was added 0.67 g of copper (I) cyanide, and the mixture was heated and stirred at 170° C. to 180° C. for 6 hours. After cooling to room temperature, the reaction mixture was poured into water, which was extracted with t-butyl methyl ether. The organic layer was washed with cold ammonia water, with water, and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 0.85 g of compound 10b (the present compound 1-283).

[1398] m.p.: 174.3° C. (decomposition)

[1399] After 0.65 g of compound lob was dissolved in 85% sulfuric acid, the solution was kept and stirred at 50° C. to 60° C. for 0.5 hour. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 0.45 g of compound 10c (the present compound 1-293).

[1400] 1H-NMR (300 MHz, CDCl3+DMSO, TMS, &dgr; (ppm)) 3.60 (3H, s), 6.40 (1H, s), 7.58 (1H, d, J=8.76 Hz), 7.84-7.95 (3H, m)

[1401] First, 0.3 g of compound 10c was added to 10 ml of a solution of boron trifluoride methanol complex in methanol, and the mixture was heated and stirred at the reflux temperature for 7 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) to give 0.22 g of compound lod (the present compound 1-303).

[1402] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.59 (3H, m), 3.92 (3H, s), 6.40 (1H, s), 7.58 (1H, d, J=9.06 Hz), 7.89 (1H, s), 8.06-8.09 (2H, m)

Production Example 11

[1403] 104

[1404] To a solution of 10.45 g of compound 11a, which had been produced according to the process as described in the JP-A 58-79960 publication, in 30 ml of N-methylpyrrolidone was added 4.56 g of copper (1) cyanide, and the mixture was kept and stirred at 110° C. to 120° C. for 6 hours. After cooling to room temperature, the reaction mixture was poured into water, which was extracted with t-butyl methyl ether. The organic layer was washed with cold ammonia water, with water, and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 5.14 g of compound [11b].

[1405] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 1.32 (3H, t, J=7.17 Hz), 4.31 (2H, q, J=7.22 Hz), 4.89 (2H, s), 7.70 (1H, d, J=1.82 Hz), 7.80 (1H, d, J=8.57 Hz), 7.93-7.95 (1H, m)

[1406] To a solution of 5.1 g of compound 11b in 50 ml of N,N-dimethylformamide was added 3.3 g of potassium carbonate, and the mixture was kept and stirred at 100° C. for 30 minutes. The reaction mixture was then cooled to room temperature and poured into water. The deposited crystals were collected by filtration. The crystals were washed with water and dried to give 4.0 g of compound 11c.

[1407] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 1.46 (3H, t, J=7.24 Hz), 4.47 (2H, q, J=7.08 Hz), 5.30 (2H, bs), 7.69 (1H, d, J=8.67 Hz), 8.16 (1H, dd,- J=8.76 Hz, 1.77 Hz), 8.34 (1H, d, J=1.87 Hz)

[1408] To a solution of 3.8 g of compound 11c in 50 ml of toluene was added 3.3 g of trichloromethyl chloroformate, and the mixture was heated and stirred at the reflux temperature of toluene for 1 hour. The reaction mixture was then concentrated to give a crude product of isocyanate.

[1409] To a suspension of 0.67 g of sodium hydride in 5 ml of N,N-dimethylformamide was added a solution of 3.1 g of ethyl 4,4,4-trifluoro-3-aminocrotonate in 5 ml of N,N-dimethylformamide below 10° C., and the mixture was stirred for 30 minutes. To the reaction mixture was then added dropwise a solution of the crude product of isocyanate obtained from compound 11c in 100 ml of tetrahydrofuran at −30° C. After completion of the dropwise addition, the mixture was warmed to room temperature and then stirred for 1 hour. To the reaction mixture was then added 4.3 g of methyl iodide, and the mixture was left undisturbed at room temperature overnight. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate 2 : 1) to give 3.80 g of compound 11d as crystals.

[1410] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 1.37 (3H, t, J=7.30 Hz), 3.36 (3H, m), 4.42 (2H, q, J=6.14 Hz), 6.14 (1H, s), 7.61 (1H, d, J=8.78 Hz), 8.26 (1H, dd, J=8.67 Hz, 2.12 Hz), 8.55 (1H, d, J=1.79 Hz)

[1411] First, 3.5 g of compound 11d was added to 20 ml of 85% sulfuric acid, and the mixture was kept and stirred at a temperature of 110° C. to 120° C. for 20 minutes. The reaction mixture was then poured into water, and the deposited crystals were collected by filtration and dried. The whole amount of the crystals obtained and 0.23 g of copper powder were added to 15 ml of quinoline, and the mixture was warmed to 120° C. to 130° C., at which temperature the mixture was kept and stirred for 1 hour. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2.5:1) to give 1.05 g of compound 11e (the present compound 1-282).

[1412] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.59-3.61 (3H, m), 6.42 (1H, s), 7.47 (1H, d, J=8.71 Hz), 8.11 (1H, s), 8.21 (1H, dd, J=8.79 Hz, 2.06 Hz), 8.48 (1H, d, J=1.85 Hz)

Production Example 12

[1413] 105

[1414] According to the process as described in the JP-A 58-79960 publication, 2-bromo-4-fluoro-5-nitrophenol was obtained from 4-fluorophenol and then used as the starting material to produce compound 12a (the present compound 1-431) according to the process as described above in Production Example 11.

[1415] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.61-3.62 (3H, m), 6.42 (1H, s), 7.24 (1H, d, J=10.4 Hz), 8.13 (1H, s), 8.33 (1H, d, J=5.79 Hz)

[1416] To a solution of 0.6 g of compound 12a in 9 ml of N,N-dimethylformamide was added 0.12 g of sodium methylsulfide below 0° C., and the mixture was stirred for 2 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, dried, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 0.24 g of compound 12b (the present compound 1-201).

[1417] 1H-NMR (300 MHz, CDCl, TMS, &dgr; (ppm)): 2.50 (s, 3H), 3.62 (3H, m), 6.43 (1H, s), 7.19 (1H, s), 8.07 (1H, s), 8.49 (1H, d, J=5.79 Hz)

Production Example 13

[1418] 106

[1419] First, 1.0 g of compound 13a and 1.15 g of 3,4,5,6-tetrahydrophthalic anhydride were added to 15 ml of acetic acid, and the mixture was heated and stirred at the reflux temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was washed with hexane: isopropanol =1: 1 (v/v) to give 1.48 g of compound 13b (the present compound 2-2001).

[1420] 1H-NMR (250 MHz, CDCl, TMS, &dgr; (ppm)): 1.75-1.95 (4H, m), 2.35-2.55 (4H, m), 6.64 (1H, m), 7.01-7.15 (4H, m), 7.63 (1H, d, J=7.0 Hz)

Production Example 14

[1421] 107

[1422] First, 0.2 g of compound 13a and 0.4 g of ethyl 3-{[1-(dimethylamino)methylidene]amino}-4,4,4-trifluoro-2-butenoate were added to 5 ml of acetic acid, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogen-carbonate solution and then with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography to give 0.05 g of compound 14a (the present compound 3-2001).

[1423] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 6.74 (1H, d, J=3.5 Hz), 7.00-7.06 (2H, m), 7.10 (1H, d, J=3.5 Hz), 7.21-7.32 (2H, m), 7.68 (1H, dd, J=1.8 Hz, 6.7 Hz), 8.40 (1H, s)

Production Example 15

[1424] 108

[1425] To a solution of 1.5 g of compound 15a in 15 ml of acetic acid was added 1.9 g of 3,4,5,6-tetrahydrophthalic anhydride, and the mixture was heated at reflux for 6 hours. After cooling to room temperature, the reaction mixture was poured into ice water, which was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogencarbonate solution and then with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography to give 3.0 g of compound 15b (the present compound 2-2004).

[1426] m.p.: 184.5° C.

Production Example 16

[1427] 109

[1428] First, 25 g of compound 16a was added to 40 ml of thionyl chloride, and the mixture was heated and stirred at the reflux temperature for 4 hours. The reaction mixture was concentrated under reduced pressure, to which residue was added 100 ml of ethanol. To the reaction mixture was then added dropwise 14 ml of pyridine under ice cooling, and the mixture was stirred at room temperature for 2 days and then left undisturbed for a half day. The reaction mixture was then concentrated, to which diluted hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogen-carbonate solution and then with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated to give 27 g of compound 16b as a crude product.

[1429] 1H-NMR (300 MHz, CDCl3, TMS, 6 &mgr;m)): 1.42 (3H, t, J=7.2 Hz), 2.66 (3H, s), 4.42 (2H, q, J=7.2 Hz), 7.43 (1H, d, J=8.0 Hz), 8.15 (1H, dd, J=1.7 Hz, 8.0 Hz), 8.60 (1H, d, J=1.7 Hz) First, 5.4 g of iron powder was added to a mixed solvent of 20 ml of acetic acid and 150 ml of water, and the mixture was heated to 70° C., to which a solution of 5.0 g of compound 16b in 20 ml of ethyl acetate was added dropwise. After completion of the dropwise addition, the mixture was left cooling to room temperature and stirred for 2 hours. Water was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogencarbonate solution, dried over anhydrous magnesium sulfate, and then concentrated to give 3.8 g of compound 16c as a crude product.

[1430] m.p.: 112.6° C.

[1431] To a solution of 1.0 g of compound 16c in 50 ml of acetic acid was added dropwise a solution of 0.42 g of sodium nitrite in 5 ml of water at 10° C. After completion of the dropwise addition, the mixture was left undisturbed at room temperature for a half day. Water was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogencarbonate solution and then with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography to give 0.5 g of compound 16d.

[1432] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 1.44 (3H, t, J=7.1 Hz), 4.44 (2H, q, J=7.1 Hz), 7.78-7.89 (2H, m), 8.16 (1H, d, J=1.1 Hz), 8.29 (1H, q, J=1.1 Hz)

[1433] To a solution of 1.0 g of compound 16d in 10 ml of N,N-dimethylformamide was added 0.2 g of sodium hydride at room temperature. After the gas evolution from the reaction mixture ceased, 1.0 g of o-(2,4-dinitrophenyl)hydroxylamine was added, and the mixture was stirred. After left undisturbed for 2 days, water was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography to give 0.36 g of compound 16e.

[1434] 1H-NMR (300 MHz, CDCl, TMS, &dgr; (ppm)): 1.42 (3H, t, J=7.2 Hz), 4.41 (2H, q, J=7.2 Hz), 5.45 (2H, bs), 7.61-7.78 (2H, m), 7.86 (1H, s), 8.28 (1H, d, J=0.8 Hz)

[1435] First, 0.15 g of compound 16e and 0.12 g of 3,4,5,6-tetrahydrophthalic anhydride were dissolved in 10 ml of acetic acid, and the solution was heated and stirred at the reflux temperature for 1 hour. After the reaction mixture was left cooling to room temperature, water was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogencarbonate solution and then with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=3:1) to give 0.09 g of compound 16f (the present compound 2-2011).

[1436] 1H-NMR (300 MHz, CDCl3, TMS, 6 (ppm)) 1.42 (3H, t, J=7.2 Hz), 1.89 (4H, m), 2.50 (4H, m), 4.42 (2H, q, J=7.2 Hz), 7.79-7.84 (1H, m), 7.91-7.96 (1H, m), 8.03 (1H, m), 8.19 (1H, d, J=1.1 Hz)

Production Example 17

[1437] 110

[1438] First, 300 mg of compound 16e and 230 mg of phenyl chloroformate were dissolved in 10 ml of tetrahydrofuran, to which 120 mg of pyridine was added at room temperature. After stirring at room temperature for 1 hour, diluted hydrochloric acid was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) to give 500 mg of compound 17a.

[1439] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 1.45 (3H, t, J=7.1 Hz), 4.45 (2H, q, J=7.1 Hz), 7.15-7.42 (5H, m), 7.76-7.80 (1H, m), 7.89-7.94 (1H, m), 8.09 (1H, s), 8.27 (1H, s)

[1440] To a mixture of 280 mg of ethyl 4,4,4-trifluoro-3-aminochrotonate and 5 ml of N,N-dimethylformamide was added 60 mg of sodium hydride at room temperature, and the mixture was stirred for 10 minutes. To the reaction solution was added dropwise a solution of 500 mg of compound 17a in 6 ml of N,N-dimethylformamide. The mixture was stirred at 80° C. for 2 hours and then left cooling to room temperature, to which 500 mg of iodomethane was added. After stirring at room temperature for 4 hours, diluted hydrochloric acid was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=5:2) to give 100 mg of compound 17b (the present compound 1-2068).

[1441] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 1.41 (3H, t, J=7.1 Hz), 3.59 (3H, m), 4.41 (2H, q, J=7.1 Hz), 6.44 (1H, s), 7.84 (1H, d, J=9.1 Hz), 7.93-7.97 (2H, m), 8.24 (1H, d, J=0.8 Hz)

Production Example 18

[1442] 111

[1443] To a solution of 2.0 g of compound 3b and 1.2 g of pyridine in 10 ml of tetrahydrofuran was added dropwise a solution of 1.6 g of ClCO2Et in 3 ml of tetrahydrofuran at 0° C. to 10° C. After stirring at room temperature for 1 hour, diluted hydrochloric acid was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was concentrated, and the residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=3:1) to give 2.7 g of compound 18a.

[1444] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 1.37 (3H, t, J=7.2 Hz), 4.33 (2H, q, J=7.2 Hz), 7.26-7.34 (2H, m), 7.48-7.58 (2H, m), 8.17 (1H, d, J=4.1 Hz)

[1445] To 15 ml of N,N-dimethylformamide was added 0.5 g of sodium hydride, to which 2.4 g of H2N(CF3)C═CHCO2Et was added dropwise under ice cooling. After stirring at room temperature for 30 minutes, a solution of compound 18a dissolved in 5 ml of N,N-dimethylformamide was added dropwise thereto. Mter heating at 100° C. for 4 hours and at 120° C. for 2 hours, the reaction mixture was cooled to room temperature. Then, 2.0 g of iodomethane was added, and the mixture was left standing overnight, to which diluted hydrochloric acid was added. The mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=3:1) to give 2.2 g of compound 18b (the present compound 1-875).

[1446] m.p.: 159.1° C.

Production Example 19

[1447] 112

[1448] First, 1.3 g of potassium tert-butoxide and 0.9 g of acetohydroxamic acid were added to 25 ml of N,N-dimethylformamide, and the mixture was stirred at room temperature for 30 minutes. A solution of 1.5 g of compound 19a dissolved in 5 ml of N,N-dimethylformamide was added dropwise thereto, and the mixture was then left standing at room temperature overnight. To the reaction mixture was added aqueous sodium chloride solution, which was extracted with ethyl acetate. The organic layer was dried with magnesium sulfate and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=2:1) to give 0.8 g of compound 19b.

[1449] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 4.38-4.64 (1H, br), 7.20-7.27 (2H, m), 7.43-7.47 (2H, m)

[1450] To 50 ml of toluene were added 2.1 g of compound 19b (produced in the same manner as described above) and 2.5 g of trichloromethyl chloroformate, and the mixture was heated at reflux for 2 hours. The reaction mixture was concentrated to give 2.5 g of compound 19c as a crude product.

[1451] To a suspension of 0.6 g of sodium hydride -in 30 ml of N,N-dimethylformamide was added 2.7 g of ethyl 4,4,4-trifluoro-3-aminochrotonate at room temperature, and the mixture was stirred for 30 minutes. To the reaction mixture was then added dropwise a solution of the whole amount of the crude product of compound 19c dissolved in 50 ml of tetrahydrofuran at 0° C. After completion of the dropwise addition, the mixture was warmed to room temperature and stirred for 3 hours, to which 2.0 g of methyl iodide was added, and the mixture was left standing overnight. The reaction mixture was then poured into diluted hydrochloric acid, which was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=3:1) to give 80 mg of compound 19d (the present compound 1-877).

[1452] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 3.57 (3H, q, J=1.2 Hz), 6.41 (1H, s), 7.36 (1H, dd, J=1.6 Hz, 8.5 Hz), 7.45 (1H, d, J=8.5 Hz), 7.71 (1H, d, J=1.6 Hz)

Production Example 20

[1453] 113

[1454] To a mixed solution of 190.0 g of compound 20a, 122.9 g of methyl chloroformate, and 150 ml of water was added dropwise aqueous sodium hydroxide solution (50 g of NaOH and 100 ml of H2O) below 10° C. After completion of the dropwise addition, the mixture was stirred for 2 hours. The crystals obtained were then collected by filtration, washed with a solution (isopropyl alcohol: water=1:1), and dried to give 160.5 g of compound 20b.

[1455] Then, 160.0 g of compound 20b was dissolved in 250 ml of concentrated sulfuric acid, to which a mixed acid (42.5 g of fuming nitric acid and 30 ml of concentrated sulfuric acid) was added dropwise below 5° C. After completion of the dropwise addition, the mixture was stirred for 2 hours. The reaction mixture was poured into ice water, and the deposited crystals were collected by filtration, washed with water, and dried to give 186.5 g of compound 20c.

[1456] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.98 (3H, s), 7.63 (1H, d, J=9.60 Hz), 8.03 (1H, d, J=6.83 Hz)

[1457] To 300 ml of water and 300 ml of ethanol was suspended 186.0 g of compound 20c, to which aqueous sodium hydroxide solution (60 g of NaOH and 120 ml of H2O) was added dropwise at room temperature. After completion of the dropwise addition, the mixture was stirred for 1 hour and then concentrated to remove the ethanol. The residue obtained was made acidic by the addition of concentrated hydrochloric acid under ice cooling, which was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and then concentrated to give 141.1 g of compound 20d.

[1458] According to the process as described in Production Example 2, compound 20e was produced from compound 20d.

[1459] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 1.32 (3H, t, J=7.11 Hz), 4.30 (2H, q, J=7.14 Hz), 4.77 (2H, s), 7.51 (1H, d, J=6.28 Hz), 7.58 (1H, d, J=9.81 Hz)

[1460] According to the process as described in Production Example 11, compound 20f was produced from compound 20e.

[1461] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 1.33 (3H, t, J=7.12 Hz), 4.30 (2H, q, J=7.12 Hz), 4.86 (2H, s), 7.52 (1H, d, J=5.66 Hz), 7.59 (1H, d, J=9.39 Hz)

[1462] First, 30 g of compound 20f was dissolved in 30 ml of N,N-dimethylformamide, to which 18.4 g of sodium acetate and 3 ml of water were added, and the mixture was kept and stirred at a temperature of 80° C. to 90° C. for 9 hours. After cooling to room temperature, diluted hydrochloric acid was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=3:1) to give 13.6 g of compound 20g.

[1463] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 1.32 (3H, t, J=7.08 Hz), 4.29 (2H, q, J=7.08 Hz), 4.79 (2H, s), 7.48 (1H, s), 7.56 (1H, s)

[1464] First, 13 g of compound 20g was dissolved in 40 ml of N,N-dimethylformamide, to which 7.3 g of potassium carbonate was added at room temperature. Then, 6.2 g of dimethylsulfuric acid was added at 30° C. to 40° C. thereto, and the mixture was stirred for 30 minutes. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with diluted hydrochloric acid, dried over magnesium sulfate, and then concentrated. The crystals obtained were washed with a solution (t-butyl methyl ether: hexane=1:2) to give 10.7 g of compound 20h.

[1465] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 1.31 (3H, t, J=7.16 Hz), 4.00 (3H, s), 4.29 (2H, q, J=7.16 Hz), 4.78 (2H, s), 7.32 (1H, s), 7.34 (1H, s)

[1466] According to the process as described in Production Example 11, compound 20i was produced from compound 20h.

[1467] According to the process as described in Production Example 11, compound 20j (the present compound 1-86) was produced from compound 20i.

[1468] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.61 (3H, m), 3.95 (3H, s), 6.42 (1H, s), 6.89 (1H, s), 8.00 (1H, s), 8.09 (1H, s)

[1469] Examples of the present compounds are shown below together with their compound numbers.

[1470] Compounds of the General Formula: 114 1 TABLE 1 Compound R2 R3 R4 A Y 1-1  H H H CH O 1-2  Cl H Cl CH O 1-3  H H H CH S 1-4  Cl H H CH O 1-5  OCH3 H H CH O 1-6  NO2 H H CH O 1-7  NH2 H H CH O 1-8  NHCH3 H H CH O 1-9  N(CH3)2 H H CH O 1-10 NHSO2CH3 H H CH O 1-11 NHCH(CH3)CO2Et H H CH O 1-12 NHCH(CH3)CO2Et H Cl CH O 1-13 N(CH3)CH(CH3)CO2Et H Cl CH O 1-14 N(CH3)SO2CH3 H Cl CH O 1-15 NHSO2CH3 H Cl CH O 1-16 NHCH(CH3)CO2Et Cl H CH O 1-17 N(CH3)CH(CH3)CO2Et Cl H CH O

[1471] 2 TABLE 2 Compound R2 R3 R4 A Y 1-18 N(CH3)SO2CH3 Cl H CH O 1-19 NHSO2CH3 Cl H CH O 1-20 NO2 H Cl CH O 1-21 NH2 H Cl CH O 1-22 NO2 Cl H CH O 1-23 NH2 Cl H CH O 1-24 NHCOCH3 H H CH O 1-25 NHCOCF3 H H CH O 1-26 NHSO2Et H H CH O 1-27 NHSO2CH2Cl H H CH O 1-28 N(CH3)COCH3 H H CH O 1-29 N(CH3)COCF3 H H CH O 1-30 N(CH3)SO2Et H H CH O 1-31 CO2C(CH3)2CO2Et H H CH O 1-32 N(CH3)SO2CH2Cl H H CH O 1-33 NHCOCH3 H Cl CH O 1-34 NHCOCF3 H Cl CH O 1-35 NHSO2Et H Cl CH O 1-36 NHSO2CH2Cl H Cl CH O 1-37 N(CH3)COCH3 Cl H CH O 1-38 N(CH3)COCF3 Cl H CH O 1-39 N(CH3)SO2Et Cl H CH O 1-40 N(CH3)SO2CH2Cl Cl H CH O 1-42 NHCH2CO2Me H H CH O 1-43 NHCH2CO2Et H H CH O

[1472] 3 TABLE 3 Compound R2 R3 R4 A Y 1-44 NHCH(CH3)COOH H H CH O 1-45 NHCH(CH3)CONH2 H H CH O 1-46 NHCH(CH3)CONHCH3 H H CH O 1-47 NHCH2CO2Me H Cl CH O 1-48 NHCH2CO2Et H Cl CH O 1-49 NHCH(CH3)COOH H Cl CH O 1-50 NHCH(CH3)CONH2 H Cl CH O 1-51 NHCH(CH3)CONHCH3 H Cl CH O 1-52 NHCH2CO2Me Cl H CH O 1-53 NHCH2CO2Et Cl H CH O 1-54 NHCH(CH3)COOH Cl H CH O 1-55 NHCH(CH3)CONH2 Cl H CH O 1-56 NHCH(CH3)CONHCH3 Cl H CH O 1-57 NHCH2CH2CH3 H H CH O 1-58 NHCH2CH═CH2 H H CH O 1-59 NHCH2C≡CH H H CH O 1-60 N(CH3)CH2CH2CH3 H H CH O 1-61 N(CH3)CH2CH═CH2 H H CH O 1-62 N(CH3)CH2C≡CH H H CH O 1-63 NHCH2CH2CH3 H Cl CH O 1-64 NHCH2CH═CH2 H Cl CH O 1-65 NHCH2C≡CH H Cl CH O 1-66 N(CH3)CH2CH2CH3 H Cl CH O 1-67 N(CH3)CH2CH═CH2 H Cl CH O 1-68 N(CH3)CH2C≡CH H Cl CH O

[1473] 4 TABLE 4 Compound R2 R3 R4 A Y 1-69 NHCH2CH2CH3 Cl H CH O 1-70 NHCH2CH═CH2 Cl H CH O 1-71 NHCH2C≡CH Cl H CH O 1-72 N(CH3)CH2CH2CH3 Cl H CH O 1-73 N(CH3)CH2CH═CH2 Cl H CH O 1-74 N(CH3)CH2C≡CH Cl H CH O 1-75 Br H H CH O 1-76 Br H Cl CH O 1-77 Br Cl H CH O 1-78 OH H H CH O 1-79 OH H Cl CH O 1-80 OH Cl H CH O 1-81 OH H NO2 CH O 1-82 OH NO2 H CH O 1-83 OCH3 H Cl CH O 1-84 OCH3 Cl H CH O 1-85 OCH3 H NO2 CH O 1-86 OCH3 NO2 H CH O 1-87 OCH(CH3)CH3 H H CH O 1-88 OCH(CH3)CH3 H Cl CH O 1-89 OCH(CH3)CH3 Cl H CH O 1-90 OCH(CH3)CH3 H NO2 CH O 1-91 OCH(CH3)CH3 NO2 H CH O 1-92 OCH2CH═CH2 H H CH O 1-93 OCH2CH═CH2 H Cl CH O

[1474] 5 TABLE 5 Compound R2 R3 R4 A Y 1-94  OCH2CH═CH2 Cl H CH O 1-95  OCH2CH═CH2 H NO2 CH O 1-96  OCH2CH═CH2 NO2 H CH O 1-97  OCH(CH3)CH═CH2 H H CH O 1-98  OCH(CH3)CH═CH2 H Cl CH O 1-99  OCH(CH3)CH═CH2 Cl H CH O 1-100 OCH(CH3)CH═CH2 H NO2 CH O 1-101 OCH(CH3)CH═CH2 NO2 H CH O 1-102 OCH2C(Cl)═CH2 H H CH O 1-103 OCH2C(Cl)═CH2 H Cl CH O 1-104 OCH2C(Cl)═CH2 Cl H CH O 1-105 OCH2C(Cl)═CH2 H NO2 CH O 1-106 OCH2C(Cl)═CH2 NO2 H CH O 1-107 OCH2C≡CH H H CH O 1-108 OCH2C≡CH H Cl CH O 1-109 OCH2C≡CH Cl H CH O 1-110 OCH2C≡CH H NO2 CH O 1-111 OCH2C≡CH NO2 H CH O 1-112 OCH(CH3)C≡CH H H CH O 1-113 OCH(CH3)C≡CH H Cl CH O 1-114 OCH(CH3)C≡CH Cl H CH O 1-115 OCH(CH3)C≡CH H NO2 CH O 1-116 OCH(CH3)C≡CH NO2 H CH O 1-117 OCH(CH3)COOH H H CH O 1-118 OCH(CH3)COOH H Cl CH O

[1475] 6 TABLE 6 Compound R2 R3 R4 A Y 1-119 OCH(CH3)COOH Cl H CH O 1-120 OCH(CH3)COOH H NO2 CH O 1-121 OCH(CH3)COOH NO2 H CH O 1-122 OCH(CH3)COOMe H H CH O 1-123 OCH(CH3)COOMe H Cl CH O 1-124 OCH(CH3)COOMe Cl H CH O 1-125 OCH(CH3)COOMe H NO2 CH O 1-126 OCH(CH3)COOMe NO2 H CH O 1-127 OCH(CH3)COOEt H H CH O 1-128 OCH(CH3)COOEt H Cl CH O 1-129 OCH(CH3)COOEt Cl H CH O 1-130 OCH(CH3)COOEt H NO2 CH O 1-131 OCH(CH3)COOEt NO2 H CH O 1-132 OCH(CH3)COOPr H H CH O 1-133 OCH(CH3)COOPr H Cl CH O 1-134 OCH(CH3)COOPr Cl H CH O 1-135 OCH(CH3)COOPr H NO2 CH O 1-136 OCH(CH3)COOPr NO2 H CH O 1-137 OCH(CH3)COO-i-Pr H H CH O 1-138 OCH(CH3)COO-i-Pr H Cl CH O 1-139 OCH(CH3)COO-i-Pr Cl H CH O 1-140 OCH(CH3)COO-i-Pr H NO2 CH O 1-141 OCH(CH3)COO-i-Pr NO2 H CH O 1-142 OCH(CH3)COOBu H H CH O 1-143 OCH(CH3)COOBu H Cl CH O

[1476] 7 TABLE 7 Compound R2 R3 R4 A Y 1-144 OCH(CH3)COOBu Cl H CH O 1-145 OCH(CH3)COOBu H NO2 CH O 1-146 OCH(CH3)COOBu NO2 H CH O 1-147 OCH(CH3)COOPen H H CH O 1-148 OCH(CH3)COOPen H Cl CH O 1-149 OCH(CH3)COOPen Cl H CH O 1-150 OCH(CH3)COOPen H NO2 CH O 1-151 OCH(CH3)COOPen NO2 H CH O 1-152 OCH(CH3)COO-c-Pen H H CH O 1-153 OCH(CH3)COO-c-Pen H Cl CH O 1-154 OCH(CH3)COO-c-Pen Cl H CH O 1-155 OCH(CH3)COO-c-Pen H NO2 CH O 1-156 OCH(CH3)COO-c-Pen NO2 H CH O 1-157 OCH(CH3)COOHex H H CH O 1-158 OCH(CH3)COOHex H Cl CH O 1-159 OCH(CH3)COOHex Cl H CH O 1-160 OCH(CH3)COOHex H NO2 CH O 1-161 OCH(CH3)COOHex NO2 H CH O 1-162 OCH(CH3)COO-c-Hex H H CH O 1-163 OCH(CH3)COO-c-Hex H Cl CH O 1-164 OCH(CH3)COO-c-Hex Cl H CH O 1-165 OCH(CH3)COO-c-Hex H NO2 CH O 1-166 OCH(CH3)COO-c-Hex NO2 H CH O 1-167 OCH(CH3)CO2CH2CO2H H H CH O 1-168 OCH(CH3)CO2CH2CO2H H Cl CH O

[1477] 8 TABLE 8 Compound R2 R3 R4 A Y 1-169 OCH(CH3)CO2CH2CO2H Cl H CH O 1-170 OCH(CH3)CO2CH2CO2H H NO2 CH O 1-171 OCH(CH3)CO2CH2CO2H NO2 H CH O 1-172 OCH(CH3)CO2CH2CO2Me H H CH O 1-173 OCH(CH3)CO2CH2CO2Me H Cl CH O 1-174 OCH(CH3)CO2CH2CO2Me Cl H CH O 1-175 OCH(CH3)CO2CH2CO2Me H NO2 CH O 1-176 OCH(CH3)CO2CH2CO2Me NO2 H CH O 1-177 OCH(CH3)CO2CH2CO2Et H H CH O 1-178 OCH(CH3)CO2CH2CO2Et H Cl CH O 1-179 OCH(CH3)CO2CH2CO2Et Cl H CH O 1-180 OCH(CH3)CO2CH2CO2Et H NO2 CH O 1-181 OCH(CH3)CO2CH2CO2Et NO2 H CH O 1-182 OCH(CH3)CO2CH(CH3)CO2H H H CH O 1-183 OCH(CH3)CO2CH(CH3)CO2H H Cl CH O 1-184 OCH(CH3)CO2CH(CH3)CO2H Cl H CH O 1-185 OCH(CH3)CO2CH(CH3)CO2H H NO2 CH O 1-186 OCH(CH3)CO2CH(CH3)CO2H NO2 H CH O 1-187 OCH(CH3)CO2CH(CH3)CO2Me H H CH O 1-188 OCH(CH3)CO2CH(CH3)CO2Me H Cl CH O 1-189 OCH(CH3)CO2CH(CH3)CO2Me Cl H CH O 1-190 OCH(CH3)CO2CH(CH3)CO2Me H NO2 CH O 1-191 OCH(CH3)CO2CH(CH3)CO2Me NO2 H CH O 1-192 OCH(CH3)CO2CH(CH3)CO2Et H H CH O 1-193 OCH(CH3)CO2CH(CH3)CO2Et H Cl CH O

[1478] 9 TABLE 9 Compound R2 R3 R4 A Y 1-194 OCH(CH3)CO2CH(CH3)CO2Et Cl H CH O 1-195 OCH(CH3)CO2CH(CH3)CO2Et H NO2 CH O 1-196 OCH(CH3)CO2CH(CH3)CO2Et NO2 H CH O 1-197 SCH3 H H CH O 1-198 SCH3 H Cl CH O 1-199 SCH3 Cl H CH O 1-200 SCH3 H NO2 CH O 1-201 SCH3 NO2 H CH O 1-202 SCH(CH3)CH3 H H CH O 1-203 SCH(CH3)CH3 H Cl CH O 1-204 SCH(CH3)CH3 Cl H CH O 1-205 SCH(CH3)CH3 H NO2 CH O 1-206 SCH(CH3)CH3 NO2 H CH O 1-207 SCHCH═CH2 H H CH O 1-208 SCHCH═CH2 H Cl CH O 1-209 SCHCH═CH2 Cl H CH O 1-210 SCHCH═CH2 H NO2 CH O 1-211 SCHCH═CH2 NO2 H CH O 1-212 SCHC≡CH H H CH O 1-213 SCHC≡CH H Cl CH O 1-214 SCHC≡CH Cl H CH O 1-215 SCHC≡CH H NO2 CH O 1-216 SCHC≡CH NO2 H CH O 1-217 SCH2COOH H H CH O 1-218 SCH2COOH H Cl CH O

[1479] 10 TABLE 10 Compound R2 R3 R4 A Y 1-219 SCH2COOH Cl H CH O 1-220 SCH2COOH H NO2 CH O 1-221 SCH2COOH NO 2 H CH O 1-222 SCH2COOMe H H CH O 1-223 SCH2COOMe H Cl CH O 1-224 SCR2COOMe Cl H CH O 1-225 SCH2COOMe H NO2 CH O 1-226 SCR2COOMe NO2 H CH O 1-227 SCH2COOEt H H CH O 1-228 SCH2COOEt H Cl CH O 1-229 SCH2COOEt Cl H CH O 1-230 SCH2COOEt H NO2 CH O 1-231 SCH2COOEt NO2 H CH O 1-232 SCH(CH3)COOH H H CH O 1-233 SCH(CH3)COOH H Cl CH O 1-234 SCH(CH3)COOH Cl H CH O 1-235 SCH(CH3)COOH H NO2 CH O 1-236 SCH(CH3)COOH NO2 H CH O 1-237 SCH(CH3)COOMe H H CH O 1-238 SCH(CH3)COOMe H Cl CH O 1-239 SCH(CH3)COOMe Cl H CH O 1-240 SCH(CH3)COOMe H NO2 CH O 1-241 SCH(CH3)COOMe NO2 H CH O 1-242 SCH(CH3)COOEt H H CH O 1-243 SCH(CH3)COOEt H Cl CH O

[1480] 11 TABLE 11 Compound R2 R3 R4 A Y 1-244 SCH(CH3)COOEt Cl H CH O 1-245 SCH(CH3)COOEt H NO2 CH O 1-246 SCH(CH3)COOEt NO2 H CH O 1-247 SCH(CH3)COO-i-Pr H H CH O 1-248 SCH(CH3)COO-i-Pr H Cl CH O 1-249 SCH(CH3)COO-i-Pr Cl H CH O 1-250 SCH(CH3)COO-i-Pr H NO2 CH O 1-251 SCH(CH3)COO-i-Pr NO2 H CH O 1-252 SCH(CH3)CO2CH2CO2H H H CH O 1-253 SCH(CH3)CO2CH2CO2H H Cl CH O 1-254 SCH(CH3)CO2CH2CO2H Cl H CH O 1-255 SCH(CH3)CO2CH2CO2H H NO2 CH O 1-256 SCH(CH3)CO2CH2CO2H NO2 H CH O 1-257 SCH(CH3)CO2CH2CO2Me H H CH O 1-258 SCH(CH3)CO2CH2CO2Me H Cl CH O 1-259 SCH(CH3)CO2CH2CO2Me Cl H CH O 1-260 SCH(CH3)CO2CH2CO2Me H NO2 CH O 1-261 SCH(CH3)CO2CH2CO2Me NO2 H CH O 1-262 SCH(CH3)CO2CH2CO2Et H H CH O 1-263 SCH(CH3)CO2CH2CO2Et H Cl CH O 1-264 SCH(CH3)CO2CH2CO2Et Cl H CH O 1-265 SCH(CH3)CO2CH2CO2Et H NO2 CH O 1-266 SCH(CH3)CO2CH2CO2Et NO2 H CH O 1-267 SCH(CH3)CO2CH(CH3)CO2H H H CH O 1-268 SCH(CH3)CO2CH(CH3)CO2H H Cl CH O

[1481] 12 TABLE 12 Compound R2 R3 R4 A Y 1-269 SCH(CH3)CO2CH(CH3)CO2H Cl H CH O 1-270 SCH(CH3)CO2CH(CH3)CO2H H NO2 CH O 1-271 SCH(CH3)CO2CH(CH3)CO2H NO2 H CH O 1-272 SCH(CH3)CO2CH(CH3)CO2Me H H CH O 1-273 SCH(CH3)CO2CH(CH3)CO2Me H Cl CH O 1-274 SCH(CH3)CO2CH(CH3)CO2Me Cl H CH O 1-275 SCH(CH3)CO2CH(CH3)CO2Me H NO2 CH O 1-276 SCH(CH3)CO2CH(CH3)CO2Me NO2 H CH O 1-277 SCH(CH3)CO2CH(CH3)CO2Et H H CH O 1-278 SCH(CH3)CO2CH(CH)CO2Et H Cl CH O 1-279 SCH(CH3)CO2CH(CH3)CO2Et Cl H CH O 1-280 SCH(CH3)CO2CH(CH3)CO2Et H NO2 CH O 1-281 SCH(CH3)CO2CH(CH3)CO2Et NO2 H CH O 1-282 H NO2 H CH O 1-283 C≡N H H CH O 1-284 C≡N H Cl CH O 1-285 C≡N Cl H CH O 1-286 C≡N H NO2 CH O 1-287 C≡N NO2 H CH O 1-288 C(═O)H H H CH O 1-289 C(═O)H H Cl CH O 1-290 C(═O)H Cl H CH O 1-291 C(═O)H H NO2 CH O 1-292 C(═O)H NO2 H CH O 1-293 C(═O)NH2 H H CH O

[1482] 13 TABLE 13 Compound R2 R3 R4 A Y 1-294 C(═O)NH2 H Cl CH O 1-295 C(═O)NH2 Cl H CH O 1-296 C(═O)NH2 H NO2 CH O 1-297 C(═O)NH2 NO2 H CH O 1-298 CO2H H H CH O 1-299 CO2H H Cl CH O 1-300 CO2H Cl H CH O 1-301 CO2H H NO2 CH O 1-302 CO2H NO2 H CH O 1-303 CO2Me H H CH O 1-304 CO2Me H Cl CH O 1-305 CO2Me Cl H CH O 1-306 CO2Me H NO2 CH O 1-307 CO2Me NO2 H CH O 1-308 CO2Et H H CH O 1-309 CO2Et H Cl CH O 1-310 CO2Et Cl H CH O 1-311 CO2Et H NO2 CH O 1-312 CO2Et NO2 H CH O 1-313 CO2CH2CO2H H H CH O 1-314 CO2CH2CO2H H Cl CH O 1-315 CO2CH2CO2H Cl H CH O 1-316 CO2CH2CO2H H NO2 CH O 1-317 CO2CH2CO2H NO2 H CH O 1-318 CO2CH2CO2Me H H CH O

[1483] 14 TABLE 14 Compound R2 R3 R4 A Y 1-319 CO2CH2CO2Me H Cl CH O 1-320 CO2CH2CO2Me Cl H CH O 1-321 CO2CH2CO2Me H NO2 CH O 1-322 CO2CH2CO2Me NO2 H CH O 1-323 CO2CH2CO2Et H H CH O 1-324 CO2CH2CO2Et H Cl CH O 1-325 CO2CH2CO2Et Cl H CH O 1-326 CO2CH2CO2Et H NO2 CH O 1-327 CO2CH2CO2Et NO2 H CH O 1-328 CO2CH(CH3)CO2H H H CH O 1-329 CO2CH(CH3)CO2H H Cl CH O 1-330 CO2CH(CH3)CO2H Cl H CH O 1-331 CO2CH(CH3)CO2H H NO2 CH O 1-332 CO2CH(CH3)CO2H NO2 H CH O 1-333 CO2CH(CH3)CO2Me H H CH O 1-334 CO2CH(CH3)CO2Me H Cl CH O 1-335 CO2CH(CH3)CO2Me Cl H CH O 1-336 CO2CH(CH3)CO2Me H NO2 CH O 1-337 CO2CH(CH3)CO2Me NO2 H CH O 1-338 CO2CH(CH3)CO2Et H H CH O 1-339 CO2CH(CH3)CO2Et H Cl CH O 1-340 CO2CH(CH3)CO2Et Cl H CH O 1-341 CO2CH(CH3)CO2Et H NO2 CH O 1-342 CO2CH(CH3)CO2Et NO2 H CH O 1-343 CO2C(CH3)2CO2H H H CH O

[1484] 15 TABLE 15 Compound R2 R3 R4 A Y 1-344 CO2C(CH3)2CO2H H Cl CH O 1-345 CO2C(CH3)2CO2H Cl H CH O 1-346 CO2C(CH3)2CO2H H NO2 CH O 1-347 CO2C(CH3)2CO2H NO2 H CH O 1-348 CO2C(CH3)2CO2Me H H CH O 1-349 CO2C(CH3)2CO2Me H Cl CH O 1-350 CO2C(CH3)2CO2Me Cl H CH O 1-351 CO2C(CH3)2CO2Me H NO2 CH O 1-352 CO2C(CH3)2CO2Me NO2 H CH O 1-353 CO2C(CH3)2CO2Et H Cl CH O 1-354 CO2C(CH3)2CO2Et Cl H CH O 1-355 CO2C(CH3)2CO2Et H NO2 CH O 1-356 CO2C(CH3)2CO2Et NO2 H CH O 1-357 CH3 H H CH O 1-358 CH3 H Cl CH O 1-359 CH3 Cl H CH O 1-360 CH3 H NO2 CH O 1-361 CH3 NO2 H CH O 1-362 CF3 H H CH O 1-363 CF3 H Cl CH O 1-364 CF3 Cl H CH O 1-365 CF3 H NO2 CH O 1-366 CF3 NO2 H CH O 1-367 CH═CHCO2H H H CH O

[1485] 16 TABLE 16 Compound R2 R3 R4 A Y 1-368 CH═CHCO2H H Cl CH O 1-369 CH═CHCO2H Cl H CH O 1-370 CH═CHCO2H H NO2 CH O 1-371 CH═CHCO2H NO2 H CH O 1-372 CH═CHCO2Me H H CH O 1-373 CH═CHCO2Me H Cl CH O 1-374 CH═CHCO2Me Cl H CH O 1-375 CH═CHCO2Me H NO2 CH O 1-376 CH═CHCO2Me NO2 H CH O 1-377 CH═CHCO2Et H H CH O 1-378 CH═CHCO2Et H Cl CH O 1-379 CH═CHCO2Et Cl H CH O 1-380 CH═CHCO2Et H NO2 CH O 1-381 CH═CHCO2Et NO2 H CH O 1-382 CH2CH2CO2H H H CH O 1-383 CH2CH2CO2H H Cl CH O 1-384 CH2CH2CO2H Cl H CH O 1-385 CH2CH2CO2H H NO2 CH O 1-386 CH2CH2CO2H NO2 H CH O 1-387 CH2CH2CO2Me H H CH O 1-388 CH2CH2CO2Me H Cl CH O 1-389 CH2CH2CO2Me Cl H CH O 1-390 CH2CH2CO2Me H NO2 CH O 1-391 CH2CH2CO2Me NO2 H CH O 1-392 CH2CH2CO2Et H H CH O

[1486] 17 TABLE 17 Compound R2 R3 R4 A Y 1-393 CH2CH2CO2Et H Cl CH O 1-394 CH2CH2CO2Et Cl H CH O 1-395 CH2CH2CO2Et H NO2 CH O 1-396 CH2CH2CO2Et NO2 H CH O 1-397 CH2CH(Cl)CO2H H H CH O 1-398 CH2CH(Cl)CO2H H Cl CH O 1-399 CH2CH(Cl)CO2H Cl H CH O 1-400 CH2CH(Cl)CO2H H NO2 CH O 1-401 CH2CH(Cl)CO2H NO2 H CH O 1-402 CH2CH(Cl)CO2Me H H CH O 1-403 CH2CH(Cl)CO2Me H Cl CH O 1-404 CH2CH(Cl)CO2Me Cl H CH O 1-405 CH2CH(Cl)CO2Me H NO2 CH O 1-406 CH2CH(Cl)CO2Me NO2 H CH O 1-407 CH2CH(Cl)CO2Et H H CH O 1-408 CH2CH(Cl)CO2Et H Cl CH O 1-409 CH2CH(Cl)CO2Et Cl H CH O 1-410 CH2CH(Cl)CO2Et H NO2 CH O 1-411 CH2CH(Cl)CO2Et NO2 H CH O 1-412 C(═O)CH3 H H CH O 1-413 C(═O)CH3 H Cl CH O 1-414 C(═O)CH3 Cl H CH O 1-415 C(═O)CH3 H NO2 CH O 1-416 C(═O)CH3 NO2 H CH O 1-417 C(CH3)═NOH H H CH O

[1487] 18 TABLE 18 Compound R2 R3 R4 A Y 1-418 C(CH3)═NOH H Cl CH O 1-419 C(CH3)═NOH Cl H CH O 1-420 C(CH3)═NOH H NO2 CH O 1-421 C(CH3)═NOH NO2 H CH O 1-422 C(CH3)═NOMe H H CH O 1-423 C(CH3)═NOMe H Cl CH O 1-424 C(CH3)═NOMe Cl H CH O 1-425 C(CH3)═NOMe H NO2 CH O 1-426 C(CH3)═NOMe NO2 H CH O 1-427 F H H CH O 1-428 F H Cl CH O 1-429 F Cl H CH O 1-430 F H NO2 CH O 1-431 F NO2 H CH O 1-432 Cl H Cl CH S 1-433 Cl H H CH S 1-434 OCH3 H H CH S 1-435 NO2 H H CH S 1-436 NH2 H H CH S 1-437 NHCH3 H H CH S 1-438 N(CH3)2 H H CH S 1-439 NHSO2CH3 H H CH S 1-440 NHCH(CH3)CO2Et H H CH S 1-441 NHCH(CH3)CO2Et H Cl CH S 1-442 N(CH3)CH(CH3)CO2Et H Cl CH S

[1488] 19 TABLE 19 Compound R2 R3 R4 A Y 1-443 N(CH3)SO2CH3 H Cl CH S 1-444 NHSO2CH3 H Cl CH S 1-445 NHCH(CH3)CO2Et Cl H CH S 1-446 N(CH3)CH(CH3)CO2Et Cl H CH S 1-447 N(CH3)SO2CH3 Cl H CH S 1-448 NHSO2CH3 Cl H CH S 1-449 NO2 H Cl CH S 1-450 NH2 H Cl CH S 1-451 NO2 Cl H CH S 1-452 NH2 Cl H CH S 1-453 NHCOCH3 H H CH S 1-454 NHCOCF3 H H CH S 1-455 NHSO2Et H H CH S 1-456 NHSO2CH2Cl H H CH S 1-457 N(CH3)COCH3 H H CH S 1-458 N(CH3)COCF3 H H CH S 1-459 N(CH3)SO2Et H H CH S 1-460 N(CH3)SO2CH2Cl H H CH S 1-461 NHCOCH3 H Cl CH S 1-462 NHCOCF3 H Cl CH S 1-463 NHSO2Et H Cl CH S 1-464 NHSO2CH2Cl H Cl CH S 1-465 N(CH3)COCH3 Cl H CH S 1-466 N(CH3)COCF3 Cl H CH S 1-467 N(CH3)SO2Et Cl H CH S

[1489] 20 TABLE 20 Compound R2 R3 R4 A Y 1-468 N(CH3)SO2CH2Cl Cl H CH S 1-469 NHCH2CO2Me H H CH S 1-470 NHCH2CO2Et H H CH S 1-471 NHCH(CH3)COOH H H CH S 1-472 NHCH(CH3)CONH2 H H CH S 1-473 NHCH(CH3)CONHCH3 H H CH S 1-474 NHCH2CO2Me H Cl CH S 1-475 NHCH2CO2Et H Cl CH S 1-476 NHCH(CH3)COOH H Cl CH S 1-477 NHCH(CH3)CONH2 H Cl CH S 1-478 NHCH(CH3)CONHCH3 H Cl CH S 1-479 NHCH2CO2Me Cl H CH S 1-480 NHCH2CO2Et Cl H CH S 1-481 NHCH(CH3)COOH Cl H CH S 1-482 NHCH(CH3)CONH2 Cl H CH S 1-483 NHCH(CH3)CONHCH3 Cl H CH S 1-484 NHCH2CH2CH3 H H CH S 1-485 NHCH2CH═CH2 H H CH S 1-486 NHCH2C≡ CH H H CH S 1-487 N(CH3)CH2CH2CH3 H H CH S 1-488 N(CH3)CH2CH═CH2 H H CH S 1-489 N(CH3)CH2C≡CH H H CH S 1-490 NHCH2CH2CH3 H Cl CH S 1-491 NHCH2CH═CH2 H Cl CH S 1-492 NHCH2C≡CH H Cl CH S

[1490] 21 TABLE 21 Compound R2 R3 R4 A Y 1-493 N(CH3)CH2CH2CH3 H Cl CH S 1-494 N(CH3)CH2CH═CH2 H Cl CH S 1-495 N(CH3)CH2C≡CH H Cl CH S 1-496 NHCH2CH2CH3 Cl H CH S 1-497 NHCH2CH═CH2 Cl H CH S 1-498 NHCH2C≡CH Cl H CH S 1-499 N(CH3)CH2CH2CH3 Cl H CH S 1-500 N(CH3)CH2CH═CH2 Cl H CH S 1-501 N(CH3)CH2C≡CH Cl H CH S 1-502 Br H H CH S 1-503 Br H Cl CH S 1-504 Br Cl H CH S 1-505 OH H H CH S 1-506 OH H Cl CH S 1-507 OH Cl H CH S 1-508 OH H NO2 CH S 1-509 OH NO2 H CH S 1-510 OCH3 H Cl CH S 1-511 OCH3 Cl H CH S 1-512 OCH3 H NO2 CH S 1-513 OCH3 NO2 H CH S 1-514 OCH(CH3)CH3 H H CH S 1-515 OCH(CH3)CH3 H Cl CH S 1-516 OCH(CH3)CH3 Cl H CH S 1-517 OCH(CH3)CH3 H NO2 CH S

[1491] 22 TABLE 22 Compound R2 R3 R4 A Y 1-518 OCH(CH3)CH3 NO2 H CH S 1-519 OCH2CH═CH2 H H CH S 1-520 OCH2CH═CH2 H Cl CH S 1-521 OCH2CH═CH2 Cl H CH S 1-522 OCH2CH═CH2 H NO2 CH S 1-523 OCH2CH═CH2 NO2 H CH S 1-524 OCH(CH3)CH═CH2 H H CH S 1-525 OCH(CH3)CH═CH2 H Cl CH S 1-526 OCH(CH3)CH═CH2 Cl H CH S 1-527 OCH(CH3)CH═CH2 H NO2 CH S 1-528 OCH(CH3)CH═CH2 NO2 H CH S 1-529 OCH2C(Cl)═CH2 H H CH S 1-530 OCH2C(Cl)═CH2 H Cl CH S 1-531 OCH2C(Cl)═CH2 Cl H CH S 1-532 OCH2C(Cl)═CH2 H NO2 CH S 1-533 OCH2C(Cl)═CH2 NO2 H CH S 1-534 OCH2C≡CH H H CH S 1-535 OCH2C≡CH H Cl CH S 1-536 OCH2C≡CH Cl H CH S 1-537 OCH2C≡CH H NO2 CH S 1-538 OCH2C≡CH NO2 H CH S 1-539 OCH(CH3)C≡CH H H CH S 1-540 OCH(CH3)C≡CH H Cl CH S 1-541 OCH(CH3)C≡CH Cl H CH S 1-542 OCH(CH3)C≡CH H NO2 CH S

[1492] 23 TABLE 23 Compound R2 R3 R4 A Y 1-543 OCH(CH3)C≡CH NO2 H CH S 1-544 OCH(CH3)COOH H H CH S 1-545 OCH(CH3)COOH H Cl CH S 1-546 OCH(CH3)COOH Cl H CH S 1-547 OCH(CH3)COOH H NO2 CH S 1-548 OCH(CH3)COOH NO2 H CH S 1-549 OCH(CH3)COOMe H H CH S 1-550 OCH(CH3)COOMe H Cl CH S 1-551 OCH(CH3)COOMe Cl H CH S 1-552 OCH(CH3)COOMe H NO2 CH S 1-553 OCH(CH3)COOMe NO2 H CH S 1-554 OCH(CH3)COOEt H H CH S 1-555 OCH(CH3)COOEt H Cl CH S 1-556 OCH(CH3)COOEt Cl H CH S 1-557 OCH(CH3)COOEt H NO2 CH S 1-558 OCH(CH3)COOEt NO2 H CH S 1-559 OCH(CH3)COOPr H H CH S 1-560 OCH(CH3)COOPr H Cl CH S 1-561 OCH(CH3)COOPr Cl H CH S 1-562 OCH(CH3)COOPr H NO2 CH S 1-563 OCH(CH3)COOPr NO2 H CH S 1-564 OCH(CH3)COO-i-Pr H H CH S 1-565 OCH(CH3)COO-i-Pr H Cl CH S 1-566 OCH(CH3)COO-i-Pr Cl H CH S 1-567 OCH(CH3)COO-i-Pr H NO2 CH S

[1493] 24 TABLE 24 Compound R2 R3 R4 A Y 1-568 OCH(CH3)COO-i-Pr NO2 H CH S 1-569 OCH(CH3)COOBu H H CH S 1-570 OCH(CH3)COOBu H Cl CH S 1-571 OCH(CH3)COOBu Cl H CH S 1-572 OCH(CH3)COOBu H NO2 CH S 1-573 OCH(CH3)COOBu NO2 H CH S 1-574 OCH(CH3)COOPen H H CH S 1-575 OCH(CH3)COOPen H Cl CH S 1-576 OCH(CH3)COOPen Cl H CH S 1-577 OCH(CH3)COOPen H NO2 CH S 1-578 OCH(CH3)COOPen NO2 H CH S 1-579 OCH(CH3)COO-c-Pen H H CH S 1-580 OCH(CH3)COO-c-Pen H Cl CH S 1-581 OCH(CH3)COO-c-Pen Cl H CH S 1-582 OCH(CH3)COO-c-Pen H NO2 CH S 1-583 OCH(CH3)COO-c-Pen NO2 H CH S 1-584 OCH(CH3)COOHex H H CH S 1-585 OCH(CH3)COOHex H Cl CH S 1-586 OCH(CH3)COOHex Cl H CH S 1-587 OCH(CH3)COOHex H NO2 CH S 1-588 OCH(CH3)COOHex NO2 H CH S 1-589 OCH(CH3)COO-c-Hex H H CH S 1-590 OCH(CH3)COO-c-Hex H Cl CH S 1-591 OCH(CH3)COO-c-Hex Cl H CH S 1-592 OCH(CH3)COO-c-Hex H NO2 CH S

[1494] 25 TABLE 25 Compound R2 R3 R4 A Y 1-593 OCH(CH3)COO-c-Hex NO2 H CH S 1-594 OCH(CH3)CO2CH2CO2H H H CH S 1-595 OCH(CH3)CO2CH2CO2H H Cl CH S 1-596 OCH(CH3)CO2CH2CO2H Cl H CH S 1-597 OCH(CH3)CO2CH2CO2H H NO2 CH S 1-598 OCH(CH3)CO2CH2CO2H NO2 H CH S 1-599 OCH(CH3)CO2CH2CO2Me H H CH S 1-600 OCH(CH3)CO2CH2CO2Me H Cl CH S 1-601 OCH(CH3)CO2CH2CO2Me Cl H CH S 1-602 OCH(CH3)CO2CH2CO2Me H NO2 CH S 1-603 OCH(CH3)CO2CH2CO2Me NO2 H CH S 1-604 OCH(CH3)CO2CH2CO2Et H H CH S 1-605 OCH(CH3)CO2CH2CO2Et H Cl CH S 1-606 OCH(CH3)CO2CH2CO2Et Cl H CH S 1-607 OCH(CH3)CO2CH2CO2Et H NO2 CH S 1-608 OCH(CH3)CO2CH2CO2Et NO2 H CH S 1-609 OCH(CH3)CO2CH(CH3)CO2H H H CH S 1-610 OCH(CH3)CO2CH(CH3)CO2H H Cl CH S 1-611 OCH(CH3)CO2CH(CH3)CO2H Cl H CH S 1-612 OCH(CH3)CO2CH(CH3)CO2H H NO2 CH S 1-613 OCH(CH3)CO2CH(CH3)CO2H NO2 H CH S 1-614 OCH(CH3)CO2CH(CH3)CO2Me H H CH S 1-615 OCH(CH3)CO2CH(CH3)CO2Me H Cl CH S 1-616 OCH(CH3)CO2CH(CH3)CO2Me Cl H CH S 1-617 OCH(CH3)CO2CH(CH3)CO2Me H NO2 CH S

[1495] 26 TABLE 26 Compound R2 R3 R4 A Y 1-618 OCH(CH3)CO2CH(CH3)CO2Me NO2 H CH S 1-619 OCH(CH3)CO2CH(CH3)CO2Et H H CH S 1-620 OCH(CH3)CO2CH(CH3)CO2Et H Cl CH S 1-621 OCH(CH3)CO2CH(CH3)CO2Et Cl H CH S 1-622 OCH(CH3)CO2CH(CH3)CO2Et H NO2 CH S 1-623 OCH(CH3)CO2CH(CH3)CO2Et NO2 H CH S 1-624 SCH3 H H CH S 1-625 SCH3 H Cl CH S 1-626 SCH3 Cl H CH S 1-627 SCH3 H NO2 CH S 1-628 SCH3 NO2 H CH S 1-629 SCH(CH3)CH3 H H CH S 1-630 SCH(CH3)CH3 H Cl CH S 1-631 SCH(CH3)CH3 Cl H CH S 1-632 SCH(CH3)CH3 H NO2 CH S 1-633 SCH(CH3)CH3 NO2 H CH S 1-634 SCHCH═CH2 H H CH S 1-635 SCHCH═CH2 H Cl CH S 1-636 SCHCH═CH2 Cl H CH S 1-637 SCHCH═CH2 H NO2 CH S 1-638 SCHCH═CH2 NO2 H CH S 1-639 SCHC≡CH H H CH S 1-640 SCHC≡CH H Cl CH S 1-641 SCHC≡CH Cl H CH S 1-642 SCHC≡CH H NO2 CH S

[1496] 27 TABLE 27 Compound R2 R3 R4 A Y 1-643 SCHC≡CH NO2 H CH S 1-644 SCH2COOH H H CH S 1-645 SCH2COOH H Cl CH S 1-646 SCH2COOH Cl H CH S 1-647 SCH2COOH H NO2 CH S 1-648 SCH2COOH NO2 H CH S 1-649 SCH2COOMe H H CH S 1-650 SCH2COOMe H Cl CH S 1-651 SCH2COOMe Cl H CH S 1-652 SCH2COOMe H NO2 CH S 1-653 SCH2COOMe NO2 H CH S 1-654 SCH2COOEt H H CH S 1-655 SCH2COOEt H Cl CH S 1-656 SCH2COOEt Cl H CH S 1-657 SCH2COOEt H NO2 CH S 1-658 SCH2COOEt NO2 H CH S 1-659 SCH(CH3)COOH H H CH S 1-660 SCH(CH3)COOH H Cl CH S 1-661 SCH(CH3)COOH Cl H CH S 1-662 SCH(CH3)COOH H NO2 CH S 1-663 SCH(CH3)COOH NO2 H CH S 1-664 SCH(CH3)COOMe H H CH S 1-665 SCH(CH3)COOMe H Cl CH S 1-666 SCH(CH3)COOMe Cl H CH S 1-667 SCH(CH3)COOMe H NO2 CH S

[1497] 28 TABLE 28 Compound R2 R3 R4 A Y 1-668 SCH(CH3)COOMe NO2 H CH S 1-669 SCH(CH3)COOEt H H CH S 1-670 SCH(CH3)COOEt H Cl CH S 1-671 SCH(CH3)COOEt Cl H CH S 1-672 SCH(CH3)COOEt H NO2 CH S 1-673 SCH(CH3)COOEt NO2 H CH S 1-674 SCH(CH3)COO-i-Pr H H CH S 1-675 SCH(CH3)COO-i-Pr H Cl CH S 1-676 SCH(CH3)COO-i-Pr Cl H CH S 1-677 SCH(CH3)COO-i-Pr H NO2 CH S 1-678 SCH(CH3)COO-i-Pr NO2 H CH S 1-679 SCH(CH3)CO2CH2CO2H H H CH S 1-680 SCH(CH3)CO2CH2CO2H H Cl CH S 1-681 SCH(CH3)CO2CH2CO2H Cl H CH S 1-682 SCH(CH3)CO2CH2CO2H H NO2 CH S 1-683 SCH(CH3)CO2CH2CO2H NO2 H CH S 1-684 SCH(CH3)CO2CH2CO2Me H H CH S 1-685 SCH(CH3)CO2CH2CO2Me H Cl CH S 1-686 SCH(CH3)CO2CH2CO2Me Cl H CH S 1-687 SCH(CH3)CO2CH2CO2Me H NO2 CH S 1-688 SCH(CH3)CO2CH2CO2Me NO2 H CH S 1-689 SCH(CH3)CO2CH2CO2Et H H CH S 1-690 SCH(CH3)CO2CH2CO2Et H Cl CH S 1-691 SCH(CH3)CO2CH2CO2Et Cl H CH S 1-692 SCH(CH3)CO2CH2CO2Et H NO2 CH S

[1498] 29 TABLE 29 Compound R2 R3 R4 A Y 1-693 SCH(CH3)CO2CH2CO2Et NO2 H CH S 1-694 SCH(CH3)CO2CH(CH3)CO2H H H CH S 1-695 SCH(CH3)CO2CH(CH3)CO2H H Cl CH S 1-696 SCH(CH3)CO2CH(CH3)CO2H Cl H CH S 1-697 SCH(CH3)CO2CH(CH3)CO2H H NO2 CH S 1-698 SCH(CH3)CO2CH(CH3)CO2H NO2 H CH S 1-699 SCH(CH3)CO2CH(CH3)CO2Me H H CH S 1-700 SCH(CH3)CO2CH(CH3)CO2Me H Cl CH S 1-701 SCH(CH3)CO2CH(CH3)CO2Me Cl H CH S 1-702 SCH(CH3)CO2CH(CH3)CO2Me H NO2 CH S 1-703 SCH(CH3)CO2CH(CH3)CO2Me NO2 H CH S 1-704 SCH(CH3)CO2CH(CH3)CO2Et H H CH S 1-705 SCH(CH3)CO2CH(CH3)CO2Et H Cl CH S 1-706 SCH(CH3)CO2CH(CH3)CO2Et Cl H CH S 1-707 SCH(CH3)CO2CH(CH3)CO2Et H NO2 CH S 1-708 SCH(CH3)CO2CH(CH3)CO2Et NO2 H CH S 1-709 H NO2 H CH S 1-710 C≡N H H CH S 1-711 C≡N H Cl CH S 1-712 C≡N Cl H CH S 1-713 C≡N H NO2 CH S 1-714 C≡N NO2 H CH S 1-715 C(═O)H H H CH S 1-716 C(═O)H H Cl CH S 1-717 C(═O)H Cl H CH S

[1499] 30 TABLE 30 Compound R2 R3 R4 A Y 1-718 C(═O)H H NO2 CH S 1-719 C(═O)H NO2 H CH S 1-720 C(═O)NH2 H H CH S 1-721 C(═O)NH2 H Cl CH S 1-722 C(═O)NH2 Cl H CH S 1-723 C(═O)NH2 H NO2 CH S 1-724 C(═O)NH2 NO2 H CH S 1-725 CO2H H H CH S 1-726 CO2H H Cl CH S 1-727 CO2H Cl H CH S 1-728 CO2H H NO2 CH S 1-729 CO2H NO2 H CH S 1-730 CO2Me H H CH S 1-731 CO2Me H Cl CH S 1-732 CO2Me Cl H CH S 1-733 CO2Me H NO2 CH S 1-734 CO2Me NO2 H CH S 1-735 CO2Et H H CH S 1-736 CO2Et H Cl CH S 1-737 CO2Et Cl H CH S 1-738 CO2Et H NO2 CH S 1-739 CO2Et NO2 H CH S 1-740 CO2CH2CO2H H H CH S 1-741 CO2CH2CO2H H Cl CH S 1-742 CO2CH2CO2H Cl H CH S

[1500] 31 TABLE 31 Compound R2 R3 R4 A Y 1-743 CO2CH2CO2H H NO2 CH S 1-744 CO2CH2CO2H NO2 H CH S 1-745 CO2CH2CO2Me H H CH S 1-746 CO2CH2CO2Me H Cl CH S 1-747 CO2CH2CO2Me Cl H CH S 1-748 CO2CH2CO2Me H NO2 CH S 1-749 CO2CH2CO2Me NO2 H CH S 1-750 CO2CH2CO2Et H H CH S 1-751 CO2CH2CO2Et H Cl CH S 1-752 CO2CH2CO2Et Cl H CH S 1-753 CO2CH2CO2Et H NO2 CH S 1-754 CO2CH2CO2Et NO2 H CH S 1-755 CO2CH(CH3)CO2H H H CH S 1-756 CO2CH(CH2)CO2H H Cl CH S 1-757 CO2CH(CH3)CO2H Cl H CH S 1-758 CO2CH(CH3)CO2H H NO2 CH S 1-759 CO2CH(CH3)CO2H NO2 H CH S 1-760 CO2CH(CH3)CO2Me H H CH S 1-761 CO2CH(CH3)CO2Me H Cl CH S 1-762 CO2CH(CH3)CO2Me Cl H CH S 1-763 CO2CH(CH3)CO2Me H NO2 CH S 1-764 CO2CH(CH3)CO2Me NO2 H CH S 1-765 CO2CH(CH3)CO2Et H H CH S 1-766 CO2CH(CH3)CO2Et H Cl CH S 1-767 CO2CH(CH3)CO2Et Cl H CH S

[1501] 32 TABLE 32 Compound R2 R3 R4 A Y 1-768 CO2CH(CH3)CO2Et H NO2 CH S 1-769 CO2CH(CH3)CO2Et NO2 H CH S 1-770 CO2C(CH3)2CO2H H H CH S 1-771 CO2C(CH3)2CO2H H Cl CH S 1-772 CO2C(CH3)2CO2H Cl H CH S 1-773 CO2C(CH3)2CO2H H NO2 CH S 1-774 CO2C(CH3)2CO2H NO2 H CH S 1-775 CO2C(CH3)2CO2Me H H CH S 1-776 CO2C(CH3)2CO2Me H Cl CH S 1-777 CO2C(CH3)2CO2Me Cl H CH S 1-778 CO2C(CH3)2CO2Me H NO2 CH S 1-779 CO2C(CH3)2CO2Me NO2 H CH S 1-780 CO2C(CH3)2CO2Et H H CH S 1-781 CO2C(CH3)2CO2Et H Cl CH S 1-782 CO2C(CH3)2CO2Et Cl H CH S 1-783 CO2C(CH3)2CO2Et H NO2 CH S 1-784 CO2C(CH3)2CO2Et NO2 H CH S 1-785 CH3 H H CH S 1-786 CH3 H Cl CH S 1-787 CH3 Cl H CH S 1-788 CH3 H NO2 CH S 1-789 CH3 NO2 H CH S 1-790 CF3 H H CH S 1-791 CF3 H Cl CH S 1-792 CF3 Cl H CH S

[1502] 33 TABLE 33 Compound R2 R3 R4 A Y 1-793 CF3 H NO2 CH S 1-794 CF3 NO2 H CH S 1-795 CH═CHCO2H H H CH S 1-796 CH═CHCO2H H Cl CH S 1-797 CH═CHCO2H Cl H CH S 1-798 CH═CHCO2H H NO2 CH S 1-799 CH═CHCO2H NO2 H CH S 1-800 CH═CHCO2Me H H CH S 1-801 CH═CHCO2Me H Cl CH S 1-802 CH═CHCO2Me Cl H CH S 1-803 CH═CHCO2Me H NO2 CH S 1-804 CH═CHCO2Me NO2 H CH S 1-805 CH═CHCO2Et H H CH S 1-806 CH═CHCO2Et H Cl CH S 1-807 CH═CHCO2Et Cl H CH S 1-808 CH═CHCO2Et H NO2 CH S 1-809 CH═CHCO2Et NO2 H CH S 1-810 CH2CH2CO2H H H CH S 1-811 CH2CH2CO2H H Cl CH S 1-812 CH2CH2CO2H Cl H CH S 1-813 CH2CH2CO2H H NO2 CH S 1-814 CH2CH2CO2H NO2 H CH S 1-815 CH2CH2CO2Me H H CH S 1-816 CH2CH2CO2Me H Cl CH S 1-817 CH2CH2CO2Me Cl H CH S

[1503] 34 TABLE 34 Compound R2 R3 R4 A Y 1-818 CH2CH2CO2Me H NO2 CH S 1-819 CH2CH2CO2Me NO2 H CH S 1-820 CH2CH2CO2Et H H CH S 1-821 CH2CH2CO2Et H Cl CH S 1-822 CH2CH2CO2Et Cl H CH S 1-823 CH2CH2CO2Et H NO2 CH S 1-824 CH2CH2CO2Et NO2 H CH S 1-825 CH2CH(Cl)CO2H H H CH S 1-826 CH2CH(Cl)CO2H H Cl CH S 1-827 CH2CH(Cl)CO2H Cl H CH S 1-828 CH2CH(Cl)CO2H H NO2 CH S 1-829 CH2CH(Cl)CO2H NO2 H CH S 1-830 CH2CH(Cl)CO2Me H H CH S 1-831 CH2CH(Cl)CO2Me H Cl CH S 1-832 CH2CH(Cl)CO2Me Cl H CH S 1-833 CH2CH(Cl)CO2Me H NO2 CH S 1-834 CH2CH(Cl)CO2Me NO2 H CH S 1-835 CH2CH(Cl)CO2Et H H CH S 1-836 CH2CH(Cl)CO2Et H Cl CH S 1-837 CH2CH(Cl)CO2Et Cl H CH S 1-838 CH2CH(Cl)CO2Et H NO2 CH S 1-839 CH2CH(Cl)CO2Et NO2 H CH S 1-840 C(═O)CH3 H H CH S 1-841 C(═O)CH3 H Cl CH S 1-842 C(═O)CH3 Cl H CH S

[1504] 35 TABLE 35 Compound R2 R3 R4 A Y 1-843 C(═O)CH3 H NO2 CH S 1-844 C(═O)CH3 NO2 H CH S 1-845 C(CH3)═NOH H H CH S 1-846 C(CH3)═NOH H Cl CH S 1-847 C(CH3)═NOH Cl H CH S 1-848 C(CH3)═NOH H NO2 CH S 1-849 C(CH3)═NOH NO2 H CH S 1-850 C(CH3)═NOMe H H CH S 1-851 C(CH3)═NOMe H Cl CH S 1-852 C(CH3)═NOMe Cl H CH S 1-853 C(CH3)═NOMe H NO2 CH S 1-854 C(CH3)═NOMe NO2 H CH S 1-855 F H H CH S 1-856 F H Cl CH S 1-857 F Cl H CH S 1-858 F H NO2 CH S 1-859 F NO2 H CH S 1-860 H H Cl CH O 1-861 H Cl H CH O 1-862 H Cl Cl CH O 1-863 H H Cl CH S 1-864 H Cl H CH S 1-865 H Cl Cl CH S 1-866 CH═NOH H Cl CH O 1-867 CH═NOH Cl H CH O

[1505] 36 TABLE 36 Compound R2 R3 R4 A Y 1-868 CH═NOH H NO2 CH O 1-869 CH═NOH NO2 H CH O 1-870 CH═NOCH3 H H CH O 1-871 CH═NO CH3 H Cl CH O 1-872 CH═NO CH3 Cl H CH O 1-873 CH═NO CH3 H NO2 CH O 1-874 CH═NO CH3 NO2 H CH O 1-875 H H H N O 1-876 H H Cl N O 1-877 H Cl H N O 1-878 H H NO2 N O 1-879 H NO2 H N O 1-880 OH H H N O 1-881 OH H Cl N O 1-882 OH Cl H N O 1-883 OH H NO2 N O 1-884 OH NO2 H N O 1-885 OCH3 H H N O 1-886 OCH3 H Cl N O 1-887 OCH3 Cl H N O 1-888 OCH3 H NO2 N O 1-889 OCH3 NO2 H N O 1-890 OCH(CH3)CH3 H H N O 1-891 OCH(CH3)CH3 H Cl N O 1-892 OCH(CH3)CH3 Cl H N O

[1506] 37 TABLE 37 Compound R2 R3 R4 A Y 1-893 OCH(CH3)CH3 H NO2 N O 1-894 OCH(CH3)CH3 NO2 H N O 1-895 OCH2C≡CH H H N O 1-896 OCH2C≡CH H Cl N O 1-897 OCH2C≡CH Cl H N O 1-898 OCH2C≡CH H NO2 N O 1-899 OCH2C≡CH NO2 H N O 1-900 OCH(CH3)C≡CH H H N O 1-901 OCH(CH3)C≡CH H Cl N O 1-902 OCH(CH3)C≡CH Cl H N O 1-903 OCH(CH3)C≡CH H NO2 N O 1-904 OCH(CH3)C≡CH NO2 H N O 1-905 OCH2CH═CH2 H H N O 1-906 OCH2CH═CH2 H Cl N O 1-907 OCH2CH═CH2 Cl H N O 1-908 OCH2CH═CH2 H NO2 N O 1-909 OCH2CH═CH2 NO2 H N O 1-910 OCH2CO2H H H N O 1-911 OCH2CO2H H Cl N O 1-912 OCH2CO2H Cl H N O 1-913 OCH2CO2H H NO2 N O 1-914 OCH2CO2H NO2 H N O 1-915 OCH2CO2Et H H N O 1-916 OCH2CO2Et H Cl N O 1-917 OCH2CO2Et Cl H N O

[1507] 38 TABLE 38 Compound R2 R3 R4 A Y 1-918 OCH2CO2Et H NO2 N O 1-919 OCH2CO2Et NO2 H N O 1-920 OCH(CH3)CO2H H H N O 1-921 OCH(CH3)CO2H H Cl N O 1-922 OCH(CH3)CO2H Cl H N O 1-923 OCH(CH3)CO2H H NO2 N O 1-924 OCH(CH3)CO2H NO2 H N O 1-925 OCH(CH3)CO2Me H H N O 1-926 OCH(CH3)CO2Me H Cl N O 1-927 OCH(CH3)CO2Me Cl H N O 1-928 OCH(CH3)CO2Me H NO2 N O 1-929 OCH(CH3)CO2Me NO2 H N O 1-930 OCH(CH3)CO2Et H H N O 1-931 OCH(CH3)CO2Et H Cl N O 1-932 OCH(CH3)CO2Et Cl H N O 1-933 OCH(CH3)CO2Et H NO2 N O 1-934 OCH(CH3)CO2Et NO2 H N O 1-935 CO2H H H N O 1-936 CO2H H Cl N O 1-937 CO2H Cl H N O 1-938 CO2H H NO2 N O 1-939 CO2H NO2 H N O 1-940 CO2Me H H N O 1-941 CO2Me H Cl N O 1-942 CO2Me Cl H N O

[1508] 39 TABLE 39 Compound R2 R3 R4 A Y 1-943 CO2Me H NO2 N O 1-944 CO2Me NO2 H N O 1-945 CO2Et H H N O 1-946 CO2Et H Cl N O 1-947 CO2Et Cl H N O 1-948 CO2Et H NO2 N O 1-949 CO2Et NO2 H N O 1-950 CO2CH(CH3)CO2 Et H H N O 1-951 CO2CH(CH3)CO2 Et H Cl N O 1-952 CO2CH(CH3)CO2 Et Cl H N O 1-953 CO2CH(CH3)CO2 Et H NO2 N O 1-954 CO2CH(CH3)CO2 Et NO2 H N O 1-955 CO2C(CH3)2CO2Et H H N O 1-956 CO2C(CH3)2CO2Et H Cl N O 1-957 CO2C(CH3)2CO2Et Cl H N O 1-958 CO2C(CH3)2CO2Et H NO2 N O 1-959 CO2C(CH3)2CO2Et NO2 H N O 1-960 C(═O)H H H N O 1-961 C(═O)H H Cl N O 1-962 C(═O)H Cl H N O 1-963 C(═O)H H NO2 N O 1-964 C(═O)H NO2 H N O 1-965 CH═CHCO2Et H H N O 1-966 CH═CHCO2Et H Cl N O 1-967 CH═CHCO2Et Cl H N O

[1509] 40 TABLE 40 Compound R2 R3 R4 A Y 1-968 CH═CHCO2Et H NO2 N O 1-969 CH═CHCO2Et NO2 H N O 1-970 CH═NOH H H N O 1-971 CH═NOH H Cl N O 1-972 CH═NOH Cl H N O 1-973 CH═NOH H NO2 N O 1-974 CH═NOH NO2 H N O 1-975 CH═NOCH3 H H N O 1-976 CH═NOCH3 H Cl N O 1-977 CH═NOCH3 Cl H N O 1-978 CH═NOCH3 H NO2 N O 1-979 CH═NOCH3 NO2 H N O 1-980 CH2CH2CO2Et H H N O 1-981 CH2CH2CO2Et H Cl N O 1-982 CH2CH2CO2Et Cl H N O 1-983 CH2CH2CO2Et H NO2 N O 1-984 CH2CH2CO2Et NO2 H N O 1-985 CH2CH(Cl)CO2Et H H N O 1-986 CH2CH(Cl)CO2Et H Cl N O 1-987 CH2CH(Cl)CO2Et Cl H N O 1-988 CH2CH(Cl)CO2Et H NO2 N O 1-989 CH2CH(Cl)CO2Et NO2 H N O 1-990 H Cl Cl N O 1-991 CF3 H Cl N O 1-992 CF3 Cl H N O

[1510] Compounds of the General Formula: 115 41 TABLE 41 Compound R2 R3 R4 A Y 1-2001 H H H CH CH 1-2002 Cl H H CH CH 1-2003 H Cl H CH CH 1-2004 H H Cl CH CH 1-2005 NO2 H H CH CH 1-2006 H NO2 H CH CH 1-2007 H H NO2 CH CH 1-2008 OH H H CH CH 1-2009 OCH3 H H CH CH 1-2010 OCH2CO2CH3 H H CH CH 1-2011 OCH2CO2C2H5 H H CH CH 1-2012 OCH(CH3)CO2CH3 H H CH CH 1-2013 OCH(CH3)CO2C2H5 H H CH CH 1-2014 OC(CH3)2CO2CH3 H H CH CH 1-2015 OC(CH3)2CO2C2H5 H H CH CH 1-2016 CO2H H H CH CH 1-2017 CO2CH3 H H CH CH 1-2018 CO2C2H5 H H CH CH 1-2019 CO2CH2CO2C2H5 H H CH CH 1-2020 CO2CH(CH3)CO2C2H5 H H CH CH 1-2021 CO2C(CH3)2CO2C2H5 H H CH CH 1-2022 OH Cl H CH CH 1-2023 OCH3 Cl H CH CH 1-2024 OCH2CO2CH3 Cl H CH CH 1-2025 OCH2CO2C2H5 Cl H CH CH

[1511] 42 TABLE 42 Compound R2 R3 R4 A Y 1-2026 OCH(CH3)CO2CH3 Cl H CH CH 1-2027 OCH(CH3)CO2C2H5 Cl H CH CH 1-2028 OC(CH3)2CO2CH3 Cl H CH CH 1-2029 OC(CH3)2CO2C2H5 Cl H CH CH 1-2030 CO2H Cl H CH CH 1-2031 CO2CH3 Cl H CH CH 1-2032 CO2C2H5 Cl H CH CH 1-2033 CO2CH2CO2C2H5 Cl H CH CH 1-2034 CO2CH(CH3)CO2C2H5 Cl H CH CH 1-2035 CO2C(CH3)2CO2C2H5 Cl H CH CH 1-2036 OH NO2 H CH CH 1-2037 OCH3 NO2 H CH CH 1-2038 OCH2CO2CH3 NO2 H CH CH 1-2039 OCH2CO2C2H5 NO2 H CH CH 1-2040 OCH(CH3)CO2CH3 NO2 H CH CH 1-2041 OCH(CH3)CO2C2H5 NO2 H CH CH 1-2042 OC(CH3)2CO2CH3 NO2 H CH CH 1-2043 OC(CH3)2CO2C2H5 NO2 H CH CH 1-2044 CO2H NO2 H CH CH 1-2045 CO2CH3 NO2 H CH CH 1-2046 CO2C2H5 NO2 H CH CH 1-2047 CO2CH2CO2C2H5 NO2 H CH CH 1-2048 CO2CH(CH3)CO2C2H5 NO2 H CH CH 1-2049 CO2C(CH3)2CO2C2H5 NO2 H CH CH 1-2050 Cl H Cl CH CH

[1512] 43 TABLE 43 Compound R2 R3 R4 A Y 1-2051 H H H N CH 1-2052 Cl H H N CH 1-2053 H Cl H N CH 1-2054 H H Cl N CH 1-2055 NO2 H H N CH 1-2056 H NO2 H N CH 1-2057 H H NO2 N CH 1-2058 OH H H N CH 1-2059 OCH3 H H N CH 1-2060 OCH2CO2CH3 H H N CH 1-2061 OCH2CO2C2H5 H H N CH 1-2062 OCH(CH3)CO2CH3 H H N CH 1-2063 OCH(CH3)CO2C2H5 H H N CH 1-2064 OC(CH3)2CO2CH3 H H N CH 1-2065 OC(CH3)2CO2C2H5 H H N CH 1-2066 CO2H H H N CH 1-2067 CO2CH3 H H N CH 1-2068 CO2C2H5 H H N CH 1-2069 CO2CH2CO2C2H5 H H N CH 1-2070 CO2CH(CH3)CO2C2H5 H H N CH 1-2071 CO2C(CH3)2CO2C2H5 H H N CH 1-2072 OH Cl H N CH 1-2073 OCH3 Cl H N CH 1-2074 OCH2CO2CH3 Cl H N CH 1-2075 OCH2CO2C2H5 Cl H N CH

[1513] 44 TABLE 44 Compound R2 R3 R4 A Y 1-2076 OCH(CH3)CO2CH3 Cl H N CH 1-2077 OCH(CH3)CO2C2H5 Cl H N CH 1-2078 OC(CH3)2CO2CH3 Cl H N CH 1-2079 OC(CH3)2CO2C2H5 Cl H N CH 1-2080 CO2H Cl H N CH 1-2081 CO2CH3 Cl H N CH 1-2082 CO2C2H5 Cl H N CH 1-2083 CO2CH2CO2C2H5 Cl H N CH 1-2084 CO2CH(CH3)CO2C2H5 Cl H N CH 1-2085 CO2C(CH3)2CO2C2H5 Cl H N CH 1-2086 OH NO2 H N CH 1-2087 OCH3 NO2 H N CH 1-2088 OCH2CO2CH3 NO2 H N CH 1-2089 OCH2CO2C2H5 NO2 H N CH 1-2090 OCH(CH3)CO2CH3 NO2 H N CH 1-2091 OCH(CH3)CO2C2H5 NO2 H N CH 1-2092 OC(CH3)2CO2CH3 NO2 H N CH 1-2093 OC(CH3)2CO2C2H5 NO2 H N CH 1-2094 CO2H NO2 H N CH 1-2095 CO2CH3 NO2 H N CH 1-2096 CO2C2H5 NO2 H N CH 1-2097 CO2CH2CO2C2H5 NO2 H N CH 1-2098 CO2CH(CH3)CO2C2H5 NO2 H N CH 1-2099 CO2C(CH3)2CO2C2H5 NO2 H N CH 1-2100 Cl H Cl N CH

[1514] 45 TABLE 45 Compound R2 R3 R4 A Y 1-2101 H H H CH N 1-2102 Cl H H CH N 1-2103 H Cl H CH N 1-2104 H H Cl CH N 1-2105 NO2 H H CH N 1-2106 H NO2 H CH N 1-2107 H H NO2 CH N 1-2108 OH H H CH N 1-2109 OCH3 H H CH N 1-2110 OCH2CO2CH3 H H CH N 1-2111 OCH2CO2C2H5 H H CH N 1-2112 OCH(CH3)CO2CH3 H H CH N 1-2113 OCH(CH3)CO2C2H5 H H CH N 1-2114 OC(CH3)2CO2CH3 H H CH N 1-2115 OC(CH3)2CO2C2H5 H H CH N 1-2116 CO2H H H CH N 1-2117 CO2CH3 H H CH N 1-2118 CO2C2H5 H H CH N 1-2119 CO2CH2CO2C2H5 H H CH N 1-2120 CO2CH(CH3)CO2C2H5 H H CH N 1-2121 CO2C(CH3)2CO2C2H5 H H CH N 1-2122 OH Cl H CH N 1-2123 OCH3 Cl H CH N 1-2124 OCH2CO2CH3 Cl H CH N 1-2125 OCH2CO2C2H5 Cl H CH N

[1515] 46 TABLE 46 Compound R2 R3 R4 A Y 1-2126 OCH(CH3)CO2CH3 Cl H CH N 1-2127 OCH(CH3)CO2C2H5 Cl H CH N 1-2128 OC(CH3)2CO2CH3 Cl H CH N 1-2129 OC(CH3)2CO2C2H5 Cl H CH N 1-2130 CO2H Cl H CH N 1-2131 CO2CH3 Cl H CH N 1-2132 CO2C2H5 Cl H CH N 1-2133 CO2CH2CO2C2H5 Cl H CH N 1-2134 CO2CH(CH3)CO2C2H5 Cl H CH N 1-2135 CO2C(CH3)2CO2C2H5 Cl H CH N 1-2136 OH NO2 H CH N 1-2137 OCH3 NO2 H CH N 1-2138 OCH2CO2CH3 NO2 H CH N 1-2139 OCH2CO2C2H5 NO2 H CH N 1-2140 OCH(CH3)CO2CH3 NO2 H CH N 1-2141 OCH(CH3)CO2C2H5 NO2 H CH N 1-2142 OC(CH3)2CO2CH3 NO2 H CH N 1-2143 OC(CH3)2CO2C2H5 NO2 H CH N 1-2144 CO2H NO2 H CH N 1-2145 CO2CH3 NO2 H CH N 1-2146 CO2C2H5 NO2 H CH N 1-2147 CO2CH2CO2C2H5 NO2 H CH N 1-2148 CO2CH(CH3)CO2C2H5 NO2 H CH N 1-2149 CO2C(CH3)2CO2C2H5 NO2 H CH N 1-2150 Cl H Cl CH N

[1516] 47 TABLE 47 Compound R2 R3 R4 A Y 1-2151 H H H N N 1-2152 Cl H H N N 1-2153 H Cl H N N 1-2154 H H Cl N N 1-2155 NO2 H H N N 1-2156 H NO2 H N N 1-2157 H H NO2 N N 1-2158 OH H H N N 1-2159 OCH3 H H N N 1-2160 OCH2CO2CH3 H H N N 1-2161 OCH2CO2C2H5 H H N N 1-2162 OCH(CH3)CO2CH3 H H N N 1-2163 OCH(CH3)CO2C2H5 H H N N 1-2164 OC(CH3)2CO2CH3 H H N N 1-2165 OC(CH3)2CO2C2H5 H H N N 1-2166 CO2H H H N N 1-2167 CO2CH3 H H N N 1-2168 CO2C2H5 H H N N 1-2169 CO2CH2CO2C2H5 H H N N 1-2170 CO2CH(CH3)CO2C2H5 H H N N 1-2171 CO2C(CH3)2CO2C2H5 H H N N 1-2172 OH Cl H N N 1-2173 OCH3 Cl H N N 1-2174 OCH2CO2CH3 Cl H N N 1-2175 OCH2CO2C2H5 Cl H N N

[1517] 48 TABLE 48 Compound R2 R3 R4 A Y 1-2176 OCH(CH3)CO2CH3 Cl H N N 1-2177 OCH(CH3)CO2C2H5 Cl H N N 1-2178 OC(CH3)2CO2CH3 Cl H N N 1-2179 OC(CH3)2CO2C2H5 Cl H N N 1-2180 CO2H Cl H N N 1-2181 CO2CH3 Cl H N N 1-2182 CO2C2H5 Cl H N N 1-2183 CO2CH2CO2C2H5 Cl H N N 1-2184 CO2CH(CH3)CO2C2H5 Cl H N N 1-2185 CO2C(CH3)2CO2C2H5 Cl H N N 1-2186 OH NO2 H N N 1-2187 OCH3 NO2 H N N 1-2188 OCH2CO2CH3 NO2 H N N 1-2189 OCH2CO2C2H5 NO2 H N N 1-2190 OCH(CH3)CO2CH3 NO2 H N N 1-2191 OCH(CH3)CO2C2H5 NO2 H N N 1-2192 OC(CH3)2CO2CH3 NO2 H N N 1-2193 OC(CH3)2CO2C2H5 NO2 H N N 1-2194 CO2H NO2 H N N 1-2195 CO2CH3 NO2 H N N 1-2196 CO2C2H5 NO2 H N N 1-2197 CO2CH2CO2C2H5 NO2 H N N 1-2198 CO2CH(CH3)CO2C2H5 NO2 H N N 1-2199 CO2C(CH3)2CO2C2H5 NO2 H N N 1-2200 Cl H Cl N N

[1518] Compounds of the General Formula: 116 49 TABLE 49 Compound R2 R3 R4 A Y 2-1  H H H CH O 2-2  Cl H Cl CH O 2-3  H H H CH S 2-4  H H H N O 2-5  Cl H Cl N O 2-6  H H H N S 2-7  OCH3 H H CH O 2-8  OCH3 H H N O 2-9  NHCH3 H H CH O 2-10 NHCH3 H H N O 2-11 OCH2CH═CH2 H H CH O 2-12 OCH2CH═CH2 H H N O 2-13 CO2CH2CO2Et H H CH O 2-14 CO2CH2CO2Et H H N O 2-15 OCH2CO2C2H5 H H CH O 2-16 OCH2CO2C2H5 H H N O 2-17 OCH(CH3)CH═CH2 H H CH O 2-18 OCH(CH3)CH═CH2 H H N O 2-19 CO2CH(CH3)CO2Et H H CH O 2-20 CO2CH(CH3)CO2Et H H N O 2-21 OCH(CH3)CO2C2H5 H H CH O 2-22 OCH(CH3)CO2C2H5 H H N O 2-23 OCH(CH3)C≡CH H H CH O 2-24 OCH(CH3)C≡CH H H N O 2-25 OCH2C≡CH H H CH O

[1519] 50 TABLE 50 Compound R2 R3 R4 A Y 2-26 OCH2C≡CH H H N O 2-27 OCH3 NO2 H CH O 2-28 OCH3 NO2 H N O 2-29 OCH3 H Cl CH O 2-30 OCH3 H Cl N O 2-31 CH2CO2CH3 H H CH O 2-32 CH2CO2CH3 H H N O 2-33 CH2CO2CH3 NO2 H CH O 2-34 CH2CO2CH3 NO2 H N O 2-35 CH2CO2CH3 H Cl CH O 2-36 CH2CO2CH3 H Cl N O 2-37 OCH(CH3)CO2C2H5 NO2 H CH O 2-38 OCH(CH3)CO2C2H5 NO2 H N O 2-39 OCH(CH3)CO2C2H5 H Cl CH O 2-40 OCH(CH3)CO2C2H5 H Cl N O 2-41 OCH2C≡CH NO2 H CH O 2-42 OCH2C≡CH NO2 H N O 2-43 OCH2C≡CH H Cl CH O 2-44 OCH2C≡CH H Cl N O 2-45 OCH(CH3)C≡CH NO2 H N O 2-46 OCH(CH3)C≡CH NO2 H CH O 2-47 OCH(CH3)C≡CH H Cl N O 2-48 OCH(CH3)C≡CH H Cl CH O 2-49 SCH(CH3)CO2C2H5 NO2 H CH O 2-50 SCH(CH3)CO2C2H5 NO2 H N O

[1520] Compounds of the General Formula: 117 51 TABLE 51 Compound R2 R3 R4 A Y 2-2001 H H H CH CH 2-2002 H H H CH N 2-2003 H H H N CH 2-2004 H H H N N 2-2005 OCH3 H H CH CH 2-2006 OCH3 H H CH N 2-2007 OCH3 H H N CH 2-2008 OCH3 H H N N 2-2009 CO2Et H H CH CH 2-2010 CO2Et H H CH N 2-2011 CO2Et H H N CH 2-2012 CO2Et H H N N 2-2013 OCH2CO2C2H5 H H CH CH 2-2014 OCH2CO2C2H5 H H CH N 2-2015 OCH2CO2C2H5 H H N CH 2-2016 OCH2CO2C2H5 H H N N 2-2017 OCH(CH3)CO2C2H5 H H CH CH 2-2018 OCH(CH3)CO2C2H5 H H CH N 2-2019 OCH(CH3)CO2C2H5 H H N CH 2-2020 OCH(CH3)CO2C2H5 H H N N 2-2021 OCH2C≡CH H H CH CH 2-2022 OCH2C≡CH H H CH N 2-2023 OCH2C≡CH H H N CH 2-2024 OCH2C≡CH H H N N 2-2025 OCH(CH3)C≡CH H H N N

[1521] Compounds of the Formula: 118 52 TABLE 52 Compound R2 R3 R4 A Y 3-1 H H H CH O 3-2 Cl H Cl CH O 3-3 H H H CH S 3-4 H H H N O 3-5 Cl H Cl N O 3-6 H H H N S 3-7 OCH3 H H CH O 3-8 OCH3 H H N O 3-9 NHCH3 H H CH O 3-10 NHOH3 H H N O 3-11 OCH2CH═CH2 H H CH O 3-12 OCH2CH═CH2 H H N O 3-13 CO2CH2CO2Et H H CH O 3-14 CO2CH2CO2Et H H N O 3-15 OCH2CO2C2H5 H H CH O 3-16 OCH2CO2C2H5 H H N O 3-17 OCH(CH3)CH═CH2 H H CH O 3-18 OCH(CH3)CH═CH2 H H N O 3-19 CO2CH(CH3)CO2Et H H CH O 3-20 CO2CH(CH3)CO2Et H H N O 3-21 OCH(CH3)CO2C2H5 H H CH O 3-22 OCH(CH3)CO2C2H5 H H N O 3-23 OCH(CH3)O≡CH H H CH O 3-24 OCH(CH3)C≡CH H H N O 3-25 OCH2C≡OH H H CH O

[1522] 53 TABLE 53 Compound R2 R3 R4 A Y 3-26 OCH2C≡CH H H N O 3-27 OCH3 NO2 H CH O 3-28 OCH3 NO2 H N O 3-29 OCH3 H Cl CH O 3-30 OCH3 H Cl N O 3-31 CH2CO2CH3 H H CH O 3-32 CH2CO2CH3 H H N O 3-33 CH2CO2CH3 NO2 H CH O 3-34 CH2CO2CH3 NO2 H N O 3-35 CH2CO2CH3 H Cl CH O 3-36 CH2CO2CH3 H Cl N O 3-37 OCH(CH3)CO2C2H5 NO2 H CH O 3-38 OCH(CH3)CO2C2H5 NO2 H N O 3-39 OCH(CH3)CO2C2H5 H Cl CH O 3-40 OCH(CH3)CO2C2H5 H Cl N O 3-41 OCH2C≡CH NO2 H CH O 3-42 OCH2C≡CH NO2 H N O 3-43 OCH2C≡CH H Cl CH O 3-44 OCH2C≡CH H Cl N O 3-45 OCH(CH3)C≡CH NO2 H N O 3-46 OCH(CH3)C≡CH NO2 H CH O 3-47 OCH(CH3)C≡CH H Cl N O 3-48 OCH(CH3)C≡CH H Cl CH O 3-49 SCH(CH3)CO2C2H5 NO2 H CH O 3-50 SCH(CH3)CO2C2H5 NO2 H N O

[1523] Compounds of the General Formula: 119 54 TABLE 54 Compound R2 R3 R4 A Y 3-2001 H H H CH CH 3-2002 H H H CH N 3-2003 H H H N CH 3-2004 H H H N N 3-2005 OCH3 H H CH CH 3-2006 OCH3 H H CH N 3-2007 OCH3 H H N CR 3-2008 OCH3 H H N N 3-2009 CO2Et H H CH CH 3-2010 CO2Et H H CH N 3-2011 CO2Et H H N CH 3-2012 CO2Et H H N N 3-2013 OCH2CO2C2H6 H H CH CR 3-2014 OCH2CO2C2H5 H H CH N 3-2015 OCH2CO2C2H5 H H N CR 3-2016 OCH2CO2C2H5 H H N N 3-2017 OCH(CH3)CO2C2H5 H H CH CR 3-2018 OCH(CH3)CO2C2H5 H H CH N 3-2019 OCH(CH3)CO2C2H5 H H N CR 3-2020 OCH(CH3)CO2C2H5 H H N N 3-2021 OCH2C≡CH H H CH CH 3-2022 OCH2C≡CH H H CH N 3-2023 OCH2C≡CH H H N CR 3-2024 OCH2C≡CH H H N N 3-2025 OCH(CH3)C≡CH H H N N

[1524] For some of the present compounds, melting points or 1H-NMR data as their physical properties are shown below.

[1525] The present compound 1-4

[1526] m.p.: 132.1° C.

[1527] The present compound 1-11

[1528] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 1.20 (3H, t, J=7.14 Hz), 1.44 (3H, d, J=6.92 Hz), 3.56 (3H, m), 4.06-4.20 (4H, m), 6.38 (1H, s), 6.42 (1H, d, J=2.33 Hz), 6.67 (1H, dd, J=8.87 Hz, 2.33 Hz), 7.32 (1H, d, J=8.87 Hz), 7.72 (1H, s)

[1529] The present compound 1-76

[1530] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.60 (3H, s), 6.40 (1H, s), 7.39 (1H, d, J=1.52 Hz), 7.51 (1H, d, J=1.52 Hz), 7.91 (1H, s)

[1531] The present compound 1-77

[1532] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.59 (3H, s), 6.40 (1H, s), 7.61 (1H, s), 7.69 (1H, s), 7.84 (1H, s)

[1533] The present compound 1-80

[1534] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 3.58-3.60 (3H, m), 5.47 (1H, s), 6.40 (1H, s), 6.92 (1H, s), 7.56 (1H, s), 7.80 (1H, s)

[1535] The present compound 1-82

[1536] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.60-3.61 (3H, m), 6.41 (1H, s), 7.02 (1H, s), 8.05 (1H, s), 8.35 (1H, s), 10.46 (1H, s)

[1537] The present compound 1-83

[1538] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.59 (3H, s), 3.80 (3H, s), 6.39 (1H, s), 6.64 (1H, d, J=2.19 Hz), 7.00 (1H, d, J=2.19 Hz), 7.85 (1H, s)

[1539] The present compound 1-84

[1540] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 3.60-3.61 (3H, m), 3.91 (3H, s), 6.41 (1H, s), 6.75 (1H, s), 7.61 (1H, s), 7.80 (1H, s)

[1541] The present compound 1-86

[1542] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.61 (3H, m), 3.95 (3H, s), 6.42 (1H, s), 6.89 (1H, s), 8.00 (1H, s), 8.09 (1H, s)

[1543] The present compound 1-128

[1544] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 1.22 (3H, t, J=7.08 Hz), 1.60 (3H, d, J=6.76 Hz), 3.58 (3H, m), 4.15-4.24 (2H, m), 4.71 (1H, q, J=6.78 Hz), 6.39 (1H, s), 6.66 (1H, d, J=2.33 Hz), 7.03 (1H, d, J=2.33 Hz), 7.86 (1H, s)

[1545] The present compound 1-129

[1546] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 1.20 (3H, t, J=7.17 Hz), 1.66 (3H, d, J=6.76 Hz), 3.57 (3H, s), 4.18 (2H, q, J=7.10 Hz), 4.72 (1H, q, J=6.85 Hz), 6.38 (1H, s), 6.83 (1H, s), 7.60 (1H, s), 7.80 (1H, s)

[1547] The present compound 1-131

[1548] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 1.20 (3H, t, J=7.20 Hz), 1.67 (3H, d, J=6.90 Hz), 3.60 (3H, m), 4.18 (2H, q, J=7.09 Hz), 4.80 (1H, q, J=6.80 Hz), 6.40 (1H, s), 6.92 (1H, s), 8.02 (1H, s), 8.09 (1H, s)

[1549] The present compound 1-246

[1550] 1H-NMR (250 MHz, CDCl3, TMS, &dgr; (ppm)): 1.13 (3H, t, J=7.07 Hz), 1.55 (3H, d, J=7.25 Hz), 3.61-3.62 (3H, m), 3.96 (1H, q, J=7.14 Hz), 4.08-4.15 (2H, m), 6.42 (1H, s), 8.10 (1H, s), 8.28 (1H, s)

[1551] The present compound 1-285

[1552] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.61 (3H, m), 6.42 (1H, s), 7.72 (1H, s), 7.73 (1H, s), 7.98 (1H, s)

[1553] The present compound 1-289

[1554] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.61-3.62 (3H, m), 6.43 (1H, s), 7.81 (1H, d, J=1.26 Hz), 7.93 (1H, d, J=1.44 Hz), 8.02 (1H, s), 10.00 (1H, s)

[1555] The present compound 1-304

[1556] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.60 (3H, s), 3.94 (3H, s), 6.41 (1H, s), 7.97 (1H, s), 7.98 (1H, d, J=1.35 Hz), 8.09 (1H,d, J=1.35 Hz)

[1557] The present compound 1-305

[1558] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.59 (3H, m), 3.93 (3H, s), 6.40 (1H, s), 7.67 (1H, s), 7.87 (1H, s), 7.89 (1H, s)

[1559] The present compound 1-358

[1560] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 2.40 (3H, s), 3.59 (3H, m), 6.40 (1H, s), 7.01 (1H, s), 7.19 (1H, s), 7.85 (1H, s)

[1561] The present compound 1-361

[1562] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 2.67 (3H, s), 3.61 (3H, m), 6.42 (1H, s), 7.27 (1H, s), 8.03 (1H, s), 8.27 (1H, s)

[1563] The present compound 1-378

[1564] m.p.: 208.2° C.

[1565] The present compound 1-861

[1566] m.p.: 135.9° C.

[1567] The present compound 1-864

[1568] m.p.: 183.8° C.

[1569] The present compound 1-871

[1570] m.p.: 193.2° C.

[1571] The present compound 1-882

[1572] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.59-3.61 (3H, m), 6.42 (1H, s), 6.98 (1H, s), 7.85 (1H, s)

[1573] The present compound 1-887

[1574] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 3.61 (3H, s), 3.96 (1H, s), 6.44 (1H, s), 6.91 (1H, s), 7.94 (1H, s)

[1575] The present compound 1-892

[1576] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 1.41 (6H, d, J=6.3 Hz), 3.60 (3H, d, J=1.1 Hz), 4.56-4.68 (1H, m), 6.43 (1H, s), 6.91 (1H, s), 7.91 (1H, s)

[1577] The present compound 1-932

[1578] 1H-NMR (300 MHz, CDCl3, TMS, &dgr; (ppm)): 1.19 (3H, t, J=7.1 Hz), 1.73 (3H, d, J=7.0), 3.59-3.61 (3H, m), 4.14-4.23 (2H, m), 4.81 (1H, q, J=7.1 Hz), 6.42 (1H, s), 6.87 (1H, s), 7.96 (1H, s)

[1579] The following are Formulation Examples in which the present compounds are indicated by their compound numbers in Tables 1 to 54 and parts are by weight.

Formulation Example 1

[1580] Fifty parts of each of the present compounds 1-1 to 1-992, 1-2001 to 1-2200, 2-1 to 2-50, 2-2001 to 2-2025, 3-1 to 3-50 and 3-2001 to 3-2025, 3 parts of calcium lignin sulfonate, 2 parts of sodium lauryl sulfate, and 45 parts of synthetic hydrated silicon oxide are well pulverized and mixed to give a wettable powder for each compound.

Formulation Example 2

[1581] Ten parts of each of the present compounds 1-1 to 1-992, 1-2001 to 1-2200, 2-1 to 2-50, 2-2001 to 2025,3-1 to 3-50 and 3-2001 to 3-2025, 14 parts of polyoxyethylene styryl phenyl ether, 6 parts of calcium dodecylbenzenesulfonate, 35 parts of xylene, and 35 parts of cyclohexanone are well mixed to an emulsifiable concentrate for each compound.

Formulation Example 3

[1582] Two parts of each of the present compounds 1-1 to 1-992, 1-2001 to 1-2200, 2-1 to 2-50, 2-2001 to 2025, 3-1 to 3-50 and 3-2001 to 3-2025, 2 parts of synthetic hydrated silicon oxide, 2 parts of calcium lignin sulfonate, 30 parts of bentonite, and 64 parts of kaolin clay are well pulverized and mixed, and the mixture is well kneaded with water, followed by granulation and drying, to give a granule for each compound.

Formulation Example 4

[1583] Twenty-five parts of each of the present compounds 1-1 to 1-992, 1-2001 to 1-2200, 2-1 to 2-50, 2-2001 to 2025, 3-1 to 3-50 and 3-2001 to 3-2025, 50 parts of 10% aqueous polyvinyl alcohol solution, and 25 parts of water are mixed and pulverized until the mean particle size reaches 5 &mgr;m or smaller to give a flowable for each compound.

Formulation Example 5

[1584] Five parts of each of the present compounds 1-1 to 1-992, 1-2001 to 1-2200, 2-1 to 2-50, 2-2001 to 2-2025, 3-1 to 3-50 and 3-2001 to 3-2025 is added to 40 parts of 10% aqueous polyvinyl alcohol solution, and the mixture is emulsified by dispersion with a homogenizer until the mean particle size reaches 10 &mgr;m or smaller, followed by addition of 55 parts of water, to give a concentrated emulsion for each compound

[1585] The following are Test Examples for demonstrating that the present compounds are useful as active ingredients of herbicides. In Test Examples, the present compounds are designated by their compound numbers in Tables 1 to 54.

Test Example 1

[1586] Cylindrical plastic pots of 10 cm in diameter and 10 cm in depth were filled with soil, seeded with velvetleaf (Abutilon theophrasti), and kept in a greenhouse for 14 days. After that, according to Formulation Example 2, compound 1-1,1-2, 1-3,1-4, 1-5,1-8, 1-9,1-10, 1-11, 1-24, 1-28, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-871, 1-877, 1-892, 1-2068, 2-4 or 2-2011 was formulated into an emulsifiable concentrate, which was diluted in a prescribed amount with water containing a spreading agent and then uniformly sprayed over the foliage of the plants with a sprayer at a ratio of 1000 liters per hectare. The pots were further kept in the greenhouse for 8 days and examined for herbicidal activity. As a result, it was found that compounds 1-1,1-2, 1-3,1-4, 1-5,1-8, 1-9,1-10, 1-11, 1-24, 1-28, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-871, 1-877, 1-892, 1-2068, 2-4 and 2-2011 completely inhibited the growth of velvetleaf at a dosage of 2000 g/ha.

Test Example 2

[1587] Cylindrical plastic pots of 10 cm in diameter and 10 cm in depth were filled with soil, seeded with velvetleaf (Abutilon theophrasti), and kept in a greenhouse for 14 days. After that, according to Formulation Example 2, compound 2-2001 or 3-2001 was formulated into an emulsifiable concentrate, which was diluted in a prescribed amount with water containing a spreading agent and then uniformly sprayed over the foliage of the plants with a sprayer at a ratio of 1000 liters per hectare. The pots were further kept in the greenhouse for 5 days and examined for herbicidal activity. As a result, it was found that compounds 2-2001 and 3-2001 completely killed velvetleaf at a dosage of 8000 g/ha.

Test Example 3

[1588] Cylindrical plastic pots of 10 cm in diameter and 10 cm in depth were filled with soil and seeded with velvetleaf (Abutilon theophrasti). According to Formulation Example 2, compound 1-1,1-2, 1-3,1-4, 1-5,1-8, 1-9,1-10, 1-11, 1-24, 1-28, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-877 or 1-892 was formulated into an emulsifiable concentrate, which was diluted in a prescribed amount with water and then uniformly sprayed over the surface of the soil in the pots with a sprayer at a ratio of 1000 liters per hectare. The pots were kept in a greenhouse for 9 days and examined for herbicidal activity. As a result, it was found that compounds 1-1,1-2, 1-3, 1-4,1-5, 1-8,1-9, 1-10, 1-11, 1-24, 1-28, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-877 and 1-892 completely inhibited the germination of velvetleaf at a dosage of 2000 g/ha.

Test Example 4

[1589] Cylindrical plastic pots of 9 cm in diameter and 11 cm of depth were filled with soil, seeded with barnyardgrass (Echinochloa oryzicola), flooded into a paddy field, and kept in a greenhouse for 12 days. According to Formulation Example 2, compound 1-1,1-2, 1-3,1-4, 1-5,1-8, 1-9,1-10, 1-11, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-864, 1-877 or 1-892 was formulated into an emulsifiable concentrate, which was diluted in a prescribed amount with water and then applied on the water surface in the pots at a ratio of 50 liters per are. The pots were further kept in the greenhouse for 9 days and examined for herbicidal activity. As a result, it was found that compounds 1-1,1-2, 1-3,1-4, 1-5,1-8, 1-9,1-10, 1-11, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-864, 1-877 and 1-892 completely inhibited the growth of barnyardgrass at a dosage of 1000 g/ha.

INDUSTRIAL APPLICABILITY

[1590] The condensed heterocyclic compounds of the present invention are useful as active ingredients of herbicides because of their excellent herbicidal activity.

Claims

1. A condensed heterocyclic compound of general formula I:

120

wherein T is carbon, the bond between T and A is a double bond, the bond between A and Y is a single bond, and Y is oxygen,;

A is nitrogen;

R1 is hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, hydroxymethyl, nitro, or cyano;

R2 is hydrogen, halogen, C1-C11 alkyl, C1-C11 haloalkyl, hydroxymethyl, nitro, cyano, —N(R9)R10, —OR11, —SR12, —SO2R13, —COX, —COOR14, —CON(R15)R16, —COR17, —C(R26)═NOR19, —C(R27)═C(R21)R22, or —CH(R23)—CH(R24)R25;

R3 is hydrogen, halogen, C1-C11 alkyl, C1-C11 haloalkyl, hydroxymethyl, nitro, cyano, —N(R50)R60, —OR61, —SR62, —SO2R63, —COX, —COOR64, —CON(R65)R66, —COR 67, —C(R76)═NOR69, —C(R77)═C(R71)R72, or —CH(R73)—CH(R74)R75;

R4 is hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, hydroxymethyl, nitro, or cyano;

wherein X is chlorine or bromine;

R9 and R59 are independently hydrogen, C1-C5 alkyl, (C1-C5 alkyl)carbonyl, or (C1-C5 alkoxy)carbonyl;

R10, R11, and R12 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C3-C10 halocycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C3-C10 alkenyl, C3-C10 haloalkenyl, C3-C10 alkynyl, C3-C10 haloalkynyl, cyano C1-C6 alkyl, (C1-C5 alkyl)carbonyl, (C1-C5 haloalkyl)carbonyl, (C3-C10 cycloalkyl)carbonyl, (C1-C5 alkyl)carbonyl C1-C5 alkyl, (C1-C5 haloalkyl)carbonyl C1-C5 alkyl, hydroxy C1-C5 alkyl, C1-C5 alkoxy C1-C5 alkyl, C1-C5 alkylthio C1-C5 alkyl, (C1-C5 alkoxy)carbonyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl, —C(R43)(R44)—C(═O)ON(R45)R46, —C(R47)(R48)—CON(R49)R50, —CH2—C(R56)═N—OR55, —CHMe—C(R58)=NOR57, (C3-C10 alkenoxy)carbonyl C1-C5 alkyl, (C3-C10 alkynoxy)carbonyl C1-C5 alkyl, phenoxycarbonyl, benzyloxycarbonyl, carboxy (C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 alkoxy)carbonyl (C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C3-C10 alkenoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C3-C10 alkynoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl, carboxy(C1-C5 alkyl)carbonyl, (C1-C10 alkoxy)carbonyl(C1-C5 alkyl)carbonyl, (C1-C10 haloalkoxy)carbonyl(C1-C5 alkyl)carbonyl, C1-C5 alkylsulfonyl, C1-C5 haloalkylsulfonyl, —SO2N(R5)R52, —CON(R53)R54, optionally substituted benzyl, or optionally substituted phenyl;

R60, R61, and R62 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C3-C10 halocycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C3-C10 alkenyl, C3-C10 haloalkenyl, C3-C10 alkynyl, C3-C10 haloalkynyl, cyano C1-C6 alkyl, (C1-C5 alkyl)carbonyl, (C1-C5 haloalkyl)carbonyl, (C3-C10 cycloalkyl)carbonyl, (C1-C5 alkyl)carbonyl C1-C5 alkyl, (C1-C5 haloalkyl)carbonyl C1-C5 alkyl, hydroxy C1-C5 alkyl, C1-C5 alkoxy C1-C5 alkyl, C1-C5 alkylthio C1-C5 alkyl, (C1-C5 alkoxy)carbonyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl, —C(R163)(R164)—C(═O)ON(R165)R166, —C(R167)(R168)—CON(R169)R170, —CH2—C(═NOR175)R176, —CHMe—C(═NOR177)R178, (C3-C10 alkenoxy)carbonyl C1-C5 alkyl, (C3-C10 alkynoxy)carbonyl C1-C5 alkyl, phenoxycarbonyl, benzyloxycarbonyl, carboxy(C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 alkoxy)carbonyl (C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl(C1-C5 alkoxy)carbonyl

C1-C5 alkyl, (C3-C10 alkenoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl,

(C3-C10 alkynoxy)carbonyl(C1-C5 alkoxy)carbonyl C1-C5 alkyl, carboxy(C1-C5 alkyl)carbonyl, (C1-C10 alkoxy)carbonyl(C1-C5 alkyl)carbonyl, (C1-C10 haloalkoxy)carbonyl(C1-C5 alkyl)carbonyl, C1-C5 alkylsulfonyl, C1-C5 haloalkylsulfonyl, —SO2N(R171)R172, —CON(R173)R174, optionally substituted benzyl, or optionally substituted phenyl;

wherein R43, R44, R163, and R164 are independently hydrogen, halogen, C1-C5 alkyl, or C1-C5 haloalkyl;

R45, R46, R165, and R166 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R45 and R46 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring, or R165 and R166 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring;

R47, R48, R167, and R168 are independently hydrogen, halogen, C1-C5 alkyl, or C1-C5 haloalkyl;

R49, R50, R169, and R170 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R49 and R50 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R169 and R170 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

R51, R52, R171, and R172 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R51 and R52 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R171 and R172 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

R53, R54, R173, and R174 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R53 and R54 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R173 and R174 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

R55, R57, R175, and R177 are independently hydrogen or C1-C3 alkyl;

R56, R58, R176, and R178 are independently hydrogen, C1-C5 alkyl, (C1-C5 alkoxy)carbonyl, (C1-C5 haloalkoxy)carbonyl, (C3-C5 cycloalkoxy)carbonyl, (C3-C5 alkenoxy)carbonyl, or (C3-C5 alkynoxy)carbonyl;

R13 is hydroxy, chlorine, C1-C10 alkyl, C1-C10 haloalkyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl, —N(R79)R80, or —OR81;

R63 hydroxy, chlorine, C1-C10 alkyl, C1-C10 haloalkyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl, —N(R179)R180, or —OR181;

wherein R79 and R179 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10cycloalkoxy)carbonyl C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl; R80 and R180 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R79 and R80 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- or 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R179 and R180 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- or 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; and R81 and R181 are independently C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl;

R14 is hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C3-C10halocycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C3-C10alkenyl, C3-C10 haloalkenyl, C3-C10alkynyl, C3-C10 haloalkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 alkenoxy)carbonyl C1-C5 alkyl, (C3-C10 alkynoxy)carbonyl C1-C5 alkyl, —N(R82)R83, optionally substituted benzyl, or optionally substituted phenyl;

R64 is hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C3-C10 halocycloalkyl, C3-C11 cycloalkyl C1-C3 alkyl, C3-C10alkenyl, C3-C10 haloalkenyl, C3-C10 alkynyl, C3-C10 haloalkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C11 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10halocycloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 alkenoxy)carbonyl C1-C5 alkyl, (C3-C10 alkynoxy)carbonyl C1-C5 alkyl, —N(R182)R183, optionally substituted benzyl, or optionally substituted phenyl;

wherein R82 and R182 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl; R83 and R183 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R82 and R83 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R182 and R183 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

R15 and R65 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, cyano C1-C6 alkyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, optionally substituted benzyl, or optionally substituted phenyl; R16 and R66 are independently hydrogen, C1-C10 alkyl, or C1-C10 haloalkyl; or R15 and R16 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R65 and R66 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

R17, R26, R27, R67, R76, and R77 are independently hydrogen, cyano,

C1-C10 alkyl, C1-C10 haloalkyl, C3-C10cycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, (C1-C6 alkoxy)carbonyl, or (C1-C6 alkoxy)carbonylmethyl;

R19 and R69 are independently hydrogen, C1-C10 alkyl, C1-C10 haloalkyl, C3-C10 cycloalkyl, C3-C10 halocycloalkyl, C3-C10 cycloalkyl C1-C3 alkyl, C3-C10 alkenyl, C3-C10 haloalkenyl, C3-C10 alkynyl, C3-C10 haloalkynyl, cyano C1-C6 alkyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, or

(C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl;

R21 and R71 are independently hydrogen, halogen, C1-C3 alkyl, or C1-C3 haloalkyl;

R22 and R25 are independently carboxy, (C1-C10 alkoxy)carbonyl,

(C1-C10 haloalkoxy)carbonyl, (C3-C10 cycloalkoxy)carbonyl, (C3-C10 halocycloalkoxy)carbonyl, carboxy(C1-C5 alkoxy)carbonyl, (C1-C10 alkoxy)carbonyl

(C1-C5 alkoxy)carbonyl, (C1-C10 haloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10 cycloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10 alkenoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10 alkynoxy)carbonyl (C1-C5 alkoxy)carbonyl, —CON(R84)R85, or —C(═O)ON(R6)R87;

R72 and R75 are independently carboxy, (C1-C10 alkoxy)carbonyl,

(C1-C10 haloalkoxy)carbonyl, (C3-C10 cycloalkoxy)carbonyl, (C3-C10 halocycloalkoxy)carbonyl, carboxy(C1-C5 alkoxy)carbonyl, (C1-C10 alkoxy)carbonyl

(C1-C5 alkoxy)carbonyl, (C1-C10 haloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10 cycloalkoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10 alkenoxy)carbonyl (C1-C5 alkoxy)carbonyl, (C3-C10 alkynoxy)carbonyl (C1-C5 alkoxy)carbonyl, —CON(R184)R185, or —C(═O)ON(R186)R187;

wherein R84 and R184 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl; R85 and R85 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R84 and R85 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R184 and R185 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

R86 and R186 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, carboxy C1-C5 alkyl, (C1-C10 alkoxy)carbonyl C1-C5 alkyl, (C1-C10 haloalkoxy)carbonyl C1-C5 alkyl, (C3-C10 cycloalkoxy)carbonyl C1-C5 alkyl, or (C3-C10 halocycloalkoxy)carbonyl C1-C5 alkyl; R87 and R187 are independently hydrogen, C1-C5 alkyl, C1-C5 haloalkyl, C3-C8 cycloalkyl, C3-C6 alkenyl, or C3-C6 alkynyl; or R86 and R87 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring; or R186 and R187 may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring;

R23, R24, R73, and R74 are independently hydrogen, halogen, C1-C3 alkyl, or C1-C3 haloalkyl; and

Q is any one group of Q1 to Q13, Q16, and Q18 to Q23 of the general formula:

121 122

wherein:

in Q1, E1 and E2 are independently C1-C6 alkyl optionally substituted with halogen, or C3-C6 cycloalkyl optionally substituted with halogen; or E1 and E2 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring (which unsaturated ring includes no aromatic rings), and the ring may optionally be substituted with methyl or halogen;

in Q2, E3 and E4 are independently C1-C6 alkyl optionally substituted with halogen, or C3-C6 cycloalkyl optionally substituted with halogen; or E3 and E4 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen; D1 and D2 are independently oxygen or sulfur; and Z1 is nitrogen or CH;

in Q3, E5 is hydrogen or C1-C6 alkyl optionally substituted with halogen; and D3 is oxygen or sulfur;

in Q4, E6 and E7 are independently hydrogen, C1-C6 alkyl optionally substituted with halogen, or C3-C6 cycloalkyl optionally substituted with halogen; or E6 and E7 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen;

in Q5, E8 and E9 are independently hydrogen, C1-C6 alkyl optionally substituted with halogen, or C3-C6 cycloalkyl optionally substituted with halogen; or E8 and E9 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen;

in Q6, E10 is hydrogen, C1-C6 alkyl optionally substituted with halogen, or C1-C3 alkoxy optionally substituted with halogen; E11 is hydrogen or C1-C6 alkyl optionally substituted with halogen; or E10 and E11 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring (which unsaturated ring includes no aromatic rings), and the ring may optionally be substituted with methyl or halogen; and E44 is halogen or C1-C3 alkyl;

in Q7, E12 is C1-C6 alkyl optionally substituted with halogen; and D4 is oxygen or sulfur;

in Q8, E13 is C1-C6 alkyl optionally substituted with halogen; and E14 is hydrogen or halogen;

in Q9, E15 is hydrogen or C1-C6 alkyl; E16 is C1-C6 alkyl optionally substituted with halogen; or E15 and E16 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring (which unsaturated ring includes no aromatic rings), and the ring may optionally be substituted with methyl or halogen;

in Q10, E17, E18, and E19 are independently hydrogen or C1-C6 alkyl; and D5 is oxygen or sulfur;

in Q11, E20 and E21 are independently hydrogen or C1-C6 alkyl; and D6 is oxygen or sulfur;

in Q12, E22 and E23 are independently hydrogen or C1-C6 alkyl;

in Q13, E24 is hydrogen or C1-C3 alkyl;

in Q16, E30 is C1-C3 alkyl optionally substituted with halogen, E31 is hydrogen or C1-C3 alkyl optionally substituted with halogen; or E30 and E31 may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO2, or NH groups in the ring (which unsaturated ring includes no aromatic rings), and the ring may optionally be substituted with methyl or halogen; and E42 is hydrogen or C1-C3 alkyl optionally substituted with halogen;

in Q18, E34 is C1-C3 alkyl optionally substituted with halogen.

2. The condensed heterocyclic compound according to claim 1, wherein Q is any one of groups Q1 to Q12.

3. The condensed heterocyclic compound according to claim 1, wherein Q is Q1, of which E1 and E2 are combined at their ends to form C2-C5 alkylene (which alkylene may optionally be substituted with methyl or halogen) or C2-C5 alkenylene (which alkenylene may optionally be substituted with methyl or halogen); or

Q is Q2, of which E3 and E4 are combined at their ends to form C2-C5 alkylene (which alkylene may optionally be substituted with methyl or halogen) or C2-C5 alkenylene (which alkenylene may optionally be substituted with methyl or halogen), and D1 and Z1 are as defined above; or

Q is Q4, of which E6 is C1-C6 alkyl optionally substituted with halogen and E7 is C1-C6 alkyl optionally substituted with halogen; or

Q is Q4, of which E6 and E7 are combined at their ends to form C2-C5 alkylene (which alkylene may optionally be substituted with methyl or halogen) or C2-C5 alkenylene (which alkenylene may optionally be substituted with methyl or halogen); or

Q is Q6, of which E44 is chlorine or bromine, E10 is C1-C6 alkyl optionally substituted with halogen, and E11 is C1-C6 alkyl optionally substituted with halogen; or

Q is Q6, of which E44 is chlorine or bromine, and E10 and E11 are combined at their ends to form C2-C5 alkylene (which alkylene may optionally be substituted with methyl or halogen) or C2-C5 alkenylene (which alkylene may optionally be substituted with methyl or halogen).

4. The condensed heterocyclic compound according to claim 1, wherein Q is selected from the group consisting of Q13, Q16, Q17 and Q18.

5. The condensed heterocyclic compound according to claim 1, wherein Q is Q16 or Q18.

6. The condensed heterocyclic compound according to claim 1, wherein Q is Q16, wherein E30 is C1-C3 alkyl optionally substituted with halogen, E31 is hydrogen or C1-C3 alkyl, and E42 is hydrogen or C1-C3 alkyl; or

Q is Q1 8, wherein E34 is C1-C3 alkyl optionally substituted with halogen; or

Q is Q19, wherein V1 is -CH2- or -CH2-CH2-, and D9 is oxygen; or

Q is Q20, wherein E35 is C1-C3 alkyl optionally substituted with halogen, Z2 is nitrogen, and V2 is —CH2—CH2— or —CH═CH—.

7. The condensed heterocyclic compound according to any one of claims 1 to 6, wherein R1 is hydrogen or halogen.

8. The condensed heterocyclic compound according to any one of claims 1 to 6, wherein R2 is hydrogen, halogen, C1-C11 alkyl, nitro, cyano,

—N(R9)R10, —OR11, —SR2, COOR4, —CON(R15)R16, —COR17, —C(R26)═NOR19—C(R27)═C(R21)R22, or —CH(R23)—R25.

9. The condensed heterocyclic compound according to any one of claims 1 to 6, wherein R3 is hydrogen, halogen, or nitro.

10. The condensed heterocyclic compound according to any one of claims 1 to 6, wherein R4 is hydrogen or halogen.

11. A herbicidal composition comprising the condensed heterocyclic compound according to any one of claims 1 to 6, and an inert carrier or diluent.

12. A method for controlling weeds, which comprises applying an effective amount of the condensed heterocyclic compound according to any one of claims 1 to 6, to weeds or to a place where weeds are growing or will grow.