Pyrazole derivatives as herbicides
Compounds of formula I 1
[0001] The present invention relates to novel, herbicidally active substituted pyridone derivatives, to a process for the preparation thereof, to compositions comprising those compounds, and to the use thereof in the control of weeds, especially in crops of useful plants, for example, cereals, maize, rice, cotton, soybean, rape, sorghum, sugar cane, sugar beet, sunflowers, vegetables, plantation crops and fodder plants, or in the inhibition of plant growth. Phenyl-pyrazole compounds having herbicidal activity are known and are described, for example, in EP-A-0 361 114, U.S. Pat. No. 5,032,165, WO 92/02509, WO 92/06962, WO 95/33728, WO 96/01254 and WO 97/00246.
[0002] Surprisingly, it has now been found that substituted pyridono-pyrazole derivatives have excellent herbicidal and growth-inhibiting properties.
[0003] The present invention accordingly relates to compounds of formula I 3
[0004] R1 is hydrogen, C1-C4alkyl, C1-C4haloalkyl, cyano-C1-C4alkyl, C3- or C4-alkenyl, C3- or C4-haloalkenyl, C3- or C4-alkynyl or C3-C6cycloalkyl;
[0005] R2 is hydrogen, C1-C4alkyl, C1-C4haloalkyl, C3-C6alkenyl, C3-C6haloalkenyl, C3-C6alkynyl, C1-C4alkyl-S(O)2— or C1-C4haloalkyl-S(O)2—;
[0006] R3 is hydrogen, C1-C4alkyl, C1-C4haloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, halogen, cyano, NH2C(S)—, nitro or amino;
[0007] n1 is 0, 1 or 2;
[0008] R4 is hydrogen, C1-C4alkyl, C1-C4haloalkyl, C3-C6alkenyl, C3-C6haloalkenyl, C3-C6alkynyl or C3-C6cycloalkyl;
[0009] R5 is hydrogen, halogen, C1-C4alkyl, C1-C4haloalkyl, cyano, nitro, amino, NH2C(O)—, NH2C(S)—, C1-C4alkylcarbonyl, C1-C6alkoxycarbonyl, C1-C4haloalkylcarbonyl, C2-C4alkenyl-carbonyl, C1-C3alkyl-CH(OH)—, OHC—, HOC(O)—, CIC(O)—, HON═CH—, C1-C4alkoxy-N═CH—, C2-C4haloalkenylcarbonyl or C2-C4alkynylcarbonyl;
[0010] R11 is hydrogen, fluorine, chlorine, bromine or methyl;
[0011] R12 is hydrogen, halogen, methyl, halomethyl, nitro, amino, hydroxy, OHC—, HOC(O)—, cyano, C1-C4alkoxycarbonyl or halomethoxy;
[0012] X1 is O, S, R20N═ or R25ON═;
[0013] R13 is hydroxy, C1-C6alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6haloalkoxy, C3-C6-haloalkenyloxy, C1-C6alkoxy-C1-C6alkyl, C3-C6alkenyloxy-C1-C6alkyl, C3-C6alkynyloxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkyl, B1-C1-C6alkoxy, R21(R22)N—, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C2-C6haloalkyl, C3-C6haloalkenyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, B1-C1-C6alkyl, OHC—, C1-C6alkylcarbonyl, C1-C6alkylcarbonyloxy, C1-C6haloalkylcarbonyl, C2-C6alkenylcarbonyl, C1-C6alkoxycarbonyl, C1-C6alkyl-S(O)2—, C1-C6haloalkyl-S(O)2—, (C1-C6alkyl)2N—N═CH—, 4
[0014] B1-CH═N—, (CH3)2N—CH═N—, (C1-C5hydroxyalkyl)-CH2—, (B1-C1-C5hydroxyalkyl)-CH2—, (B1-C1-C5haloalkyl)-CH2—, (hydroxy-C1-C5alkyl)-O— or (B1-C1-C5hydroxyalkyl)-O—;
[0015] B1 is cyano, OHC—, HOC(O)—, C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, C3-C6alkenyloxycarbonyl, C3-C6alkynyloxycarbonyl, benzyloxycarbonyl, benzyloxycarbonyl mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl, benzylthio-C(O)—, benzylthio-C(O)— mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl, C1-C6haloalkoxycarbonyl, C1-C6alkylthio-C(O)—, R26(R27)NC(O)—, phenyl, phenyl mono- to tri-substituted by halogen, C1-C4alkyl or by C1-C4haloalkyl, C1-C6-alkyl-S(O)2—, C1-C6alkyl-S(O)—, C1-C6alkylthio, C3-C6cycloalkyl, C1-C6alkoxy, C3-C6alkenylthio or C3-C6alkynylthio;
[0016] R20 is hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C2-C6haloalkyl, cyano, R23(R24)N—, C1-C6alkoxycarbonyl, C3-C6alkenyloxycarbonyl, C3-C6alkynyloxycarbonyl, C2-C6haloalkoxycarbonyl, OHC—, C1-C6alkylcarbonyl, C1-C6haloalkylcarbonyl, C1-C6alkyl-S(O)2—, C1-C6haloalkyl-S(O)2—, phenyl, phenyl mono- to tri-substituted by halogen, C1-C4alkyl or by C1-C4haloalkyl, phenyl-C1-C6alkyl, or phenyl-C1-C6alkyl mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl;
[0017] R21 and R22 are each independently hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6-haloalkyl, C3-C6haloalkenyl, C3-C6cycloalkyl, C1-C6alkoxy-C1-C6alkyl, OHC—, C1-C6alkylcarbonyl, C1-C6haloalkylcarbonyl, C1-C6alkyl-S(O)2— or C1-C6haloalkyl-S(O)2—;
[0018] R23 and R24 are each independently as defined for R21;
[0019] R25 is hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C3-C6haloalkenyl, C1-C6alkoxy-C1-C6alkyl, benzyl, C1-C6alkyl-S(O)2— or C1-C6haloalkyl-S(O)2—;
[0020] R26 and R27 are each independently hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C3-C6haloalkenyl, phenyl, phenyl mono- to tri-substituted by halogen, C1-C4alkyl or by C1-C4haloalkyl, benzyl, or benzyl mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl; or
[0021] X1 and R13 together form a group ═N—Y— wherein Y is bonded to the ring nitrogen atom;
[0022] Y is —C(R31)(R32)—CH2—, —C(R31)(R32)—O—, —C(R31)(R32)—CH2—CH2—, —C(R31)(R32)—CH2—O—, —O—CH2—, —O—CH2—CH2—, —O—CH═CH—, —N(R33)—CH2—, —N(R33)—CH2—CH2—, —N(R33)—CH═CH—, —N(R33)—C(X3)—CH2—, —C(X3)—CH2—, —C(X3)—CH2—CH2—, —C(X3)—CH2—O—, —C(X3)—O—, —C(R34)═CH—, —C(R31)(R32)—CH═CH—, —C(R34)═N—, —C(R31)(R32)—CH═N—, —C(R31)(R32)—N═CH—, —C(X3)—CH═CH—, —N═N—, —C(R31)(R32)—C(O)—, —C(R31)(R32)—C(S)—, —C(R31)(R32)—CH2—C(O)—, —C(R31)(R32)—CH2—C(S)—, —N(R33)—C(O)—, —N(R33)—C(S)—, —N(R33)—CH2—C(O)—, —N(R33)—CH2—C(S)—, —O—C(O)—, —O—C(S)—, —C(R34)═CH—C(O)— or —C(R34)═CH—C(S)—, the right-hand end of the bridge members in the above definitions of Y being bonded to the ring nitrogen atom;
[0023] R31 is hydrogen, C1-C6alkyl or C1-C6haloalkyl;
[0024] R32 is hydrogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl, cyano-C1-C6alkyl, hydroxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C3-C6alkenyloxy-C1-C6alkyl, C3-C6alkynyloxy-C1-C6alkyl, C1-C6alkylcarbonyloxy-C1-C6alkyl, C1-C6haloalkylcarbonyloxy-C1-C6alkyl, carboxyl, C1-C6alkoxycarbonyl, C3-C6alkenyloxycarbonyl, C3-C6alkynyloxycarbonyl, C1-C6haloalkoxycarbonyl, C3-C6cycloalkoxycarbonyl, C1-C4alkoxy-C1-C6alkoxycarbonyl, C1-C6alkyl-NHC(O)—, (C1-C6alkyl)2NC(O)—, C3-C6alkenyl-NHC(O)—, C1-C6alkyl-(C3-C6-alkenyl)NC(O)—, C3-C6alkynyl-NHC(O)—, aminocarbonyl, C1-C6alkylthio-C(O)—, C3-C6-alkenylthio-C(O)—, C3-C6alkynylthio-C(O)—, benzyloxycarbonyl, benzyloxycarbonyl mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl, phenoxycarbonyl, C1-C6alkyl-S(O)2NHC(O)—, C1-C6alkyl-S(O)2(C3-C6alkenyl)N—C(O)—, C1-C6haloalkyl-S(O)2NHC(O)—, HON═CH—, C1-C6alkoxy-N═CH—, C3-C6alkenyloxy-N═CH—, C3-C6alkynyloxy-N═CH—, HOC(O)—C1-C6alkyl, C1-C6alkoxycarbonyl-C1-C6alkyl, C3-C6alkenyloxycarbonyl-C1-C6alkyl, C3-C6alkynyloxycarbonyl-C1-C6alkyl, C1-C6alkylcarbonyl, CIC(O)—, H2NC(S)—, OHC—, cyano, phenyl, phenyl mono- to tri-substituted by halogen, C1-C4alkyl or by C1-C4-haloalkyl, phenyl-C1-C6alkyl, or phenyl-C1-C6alkyl mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl;
[0025] X3 is O, S, R20N═ or R25ON═;
[0026] R33 is hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C3-C6haloalkenyl, C3-C6cycloalkyl, C1-C6alkylcarbonyl, C1-C6haloalkylcarbonyl, C1-C6alkyl-S(O)2— or B2-C1-C6-alkyl;
[0027] B2 is cyano, HOC(O)—, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl or C1-C6alkoxy; and
[0028] R34 is as defined for R32 or is halogen, C1-C6alkoxy, C3-C6alkenyloxy, C1-C6haloalkoxy, C1-C6alkylthio, C1-C6alkyl-S(O)— or C1-C6alkyl-S(O)2—,
[0029] and also to the pyrazole N-oxides, agrochemically acceptable salts and stereoisomers of those compounds of formula I.
[0030] In the above definitions, halogen is to be understood as meaning iodine or, preferably, fluorine, chlorine or bromine.
[0031] The alkyl, alkenyl and alkynyl groups in the substituent definitions may be straight-chain or branched, this applying also to the alkyl, alkenyl and alkynyl moiety of the alkylcarbonyl, hydroxyalkyl, cyanoalkyl, alkoxyalkyl, alkoxyalkoxyalkyl, alkylthio, alkylthio-C(O)—, alkylsulfonyl, alkylaminocarbonyl, dialkylaminocarbonyl, B1-alkyl and HOC(O)-alkyl groups. Alkyl groups are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl and the various isomers of pentyl and hexyl. Methyl, ethyl, n-propyl, isopropyl and n-butyl are preferred.
[0032] There may be mentioned as examples of alkenyl radicals vinyl, allyl, methallyl, 1-methylvinyl, but-2-en-1-yl, pentenyl and 2-hexenyl, with preference being given to alkenyl radicals having a chain length of from 3 to 5 carbon atoms.
[0033] There may be mentioned as examples of alkynyl radicals ethynyl, propargyl, 1-methylpropargyl, 3-butynyl, but-2-yn-1-yl, 2-methylbutyn-2-yl, but-3-yn-2-yl, 1-pentynyl, pent-4-yn-1-yl and 2-hexynyl, with preference being given to alkynyl radicals having a chain length of from 2 to 4 carbon atoms.
[0034] Suitable haloalkyl radicals are alkyl groups that are mono- or poly-substituted, especially mono- to tri-substituted, by halogen, halogen being in particular iodine or especially fluorine, chlorine or bromine, for example fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2-chloroethyl, 2,2-dichloroethyl, 2,2,2-trifluoroethyl and 2,2,2-trichloroethyl.
[0035] Suitable haloalkenyl radicals are alkenyl groups mono- or poly-substituted by halogen, halogen being in particular bromine, iodine or especially fluorine or chlorine, for example 2- or 3-fluoropropenyl, 2- or 3-chloropropenyl, 2- or 3-bromopropenyl, 2,3,3-trifluoropropenyl, 2,3,3-trichloropropenyl, 4,4,4-trifluorobut-2-en-1-yl and 4,4,4-trichlorobut-2-en-1-yl. Of the alkenyl radicals mono-, di- or tri-substituted by halogen, preference is given to those having a chain length of 3 or 4 carbon atoms. The alkenyl groups may be substituted by halogen at saturated or unsaturated carbon atoms.
[0036] Alkylsulfonyl is, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl or an isomer of pentylsulfonyl or hexylsulfonyl; preferably methylsulfonyl or ethylsulfonyl.
[0037] Haloalkylsulfonyl is, for example, fluoromethylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl, chloromethylsulfonyl, trichloromethylsulfonyl, 2-fluoroethylsulfonyl, 2,2,2-trifluoroethylsulfonyl or 2,2,2-trichloroethylsulfonyl.
[0038] Alkenylsulfonyl is, for example, allylsulfonyl, methallylsulfonyl, but-2-en-1-ylsulfonyl, pentenylsulfonyl or 2-hexenylsulfonyl.
[0039] Haloalkenylsulfonyl is, for example, 2- or 3-fluoropropenylsulfonyl, 2- or 3-chloropropenylsulfonyl, 2- or 3-bromopropenylsulfonyl, 2,3,3-trifluoropropenylsulfonyl, 2,3,3-trichloropropenylsulfonyl, 4,4,4-trifluorobut-2-en-1-ylsulfonyl or 4,4,4-trichlorobut-2-en-1-ylsulfonyl.
[0040] Cyanoalkyl is, for example, cyanomethyl, cyanoethyl, cyanoeth-1-yl or cyanopropyl.
[0041] Hydroxyalkyl is, for example, hydroxymethyl, 2-hydroxyethyl or 3-hydroxypropyl.
[0042] Alkylamino is, for example, methylamino, ethylamino or an isomer of propyl- or butyl-amino.
[0043] Dialkylamino is, for example, dimethylamino, diethylamino or an isomer of dipropyl- or dibutyl-amino.
[0044] Alkenylamino is, for example, allylamino, methallylamino or but-2-en-1-ylamino.
[0045] Alkynylamino is, for example, propargylamino or 1 -methylpropargylamino.
[0046] Haloalkylamino is, for example, chloroethylamino, trifluoroethylamino or 3-chloropropylamino.
[0047] Di(haloalkyl)amino is, for example, di(2-chloroethyl)amino.
[0048] Alkylcarbonyl is especially acetyl or propionyl.
[0049] Haloalkylcarbonyl is especially trifluoroacetyl, trichloroacetyl, 3,3,3-trifluoropropionyl or 3,3,3-trichloropropionyl.
[0050] Alkenylcarbonyl is especially vinylcarbonyl, allylcarbonyl, methallylcarbonyl, but-2-en-1-yl-carbonyl, pentenylcarbonyl or 2-hexenylcarbonyl.
[0051] Alkynylcarbonyl is especially acetylenecarbonyl, propargylcarbonyl, 1-methylpropargylcarbonyl, 3-butynylcarbonyl, but-2-yn-1-ylcarbonyl or pent-4-yn-1-ylcarbonyl.
[0052] Alkoxy is, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy or an isomer of pentyloxy or hexyloxy.
[0053] Alkenyloxy is, for example, allyloxy, methallyloxy or but-2-en-1-yloxy.
[0054] Alkynyloxy is, for example, propargyloxy or 1-methylpropargyloxy.
[0055] Alkoxyalkyl is, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n-propoxymethyl, n-propoxyethyl, isopropoxymethyl or isopropoxyethyl.
[0056] Alkenyloxyalkyl is, for example, allyloxyalkyl, methallyloxyalkyl or but-2-en-1-yloxyalkyl.
[0057] Alkynyloxyalkyl is, for example, propargyloxyalkyl or 1-methylpropargyloxyalkyl.
[0058] Alkoxycarbonyl is, for example, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl or n-butoxycarbonyl, preferably methoxycarbonyl or ethoxycarbonyl.
[0059] Alkenyloxycarbonyl is, for example, allyloxycarbonyl, methallyloxycarbonyl, but-2-en-1-yl-oxycarbonyl, pentenyloxycarbonyl or 2-hexenyloxycarbonyl.
[0060] Alkynyloxycarbonyl is, for example, propargyloxycarbonyl, 3-butynyloxycarbonyl, but-2-yn-1-yloxycarbonyl or 2-methylbutyn-2-yloxycarbonyl.
[0061] Alkoxyalkoxycarbonyl is, for example, methoxymethoxycarbonyl, ethoxymethoxycarbonyl, ethoxyethoxycarbonyl, propoxymethoxycarbonyl, propoxyethoxycarbonyl, propoxypropoxycarbonyl or butoxyethoxycarbonyl.
[0062] Haloalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy or 2,2,2-trichloroethoxy.
[0063] Of the alkenyl radicals mono-, di- or tri-substituted by halogen, preference is given to those having a chain length of 3 or 4 carbon atoms. The alkenyloxy groups may be substituted by halogen at saturated or unsaturated carbon atoms.
[0064] Suitable haloalkenyloxy radicals are alkenyloxy groups mono- or poly-substituted by halogen, halogen being in particular bromine, iodine or especially fluorine or chlorine, for example 2- or 3-fluoropropenyloxy, 2- or 3-chloropropenyloxy, 2- or 3-bromopropenyloxy, 2,3,3-trifluoropropenyloxy, 2,3,3-trichloropropenyloxy, 4,4,4-trifluoro-but-2-en-1-yloxy and 4,4,4-trichlorobut-2-en-1-yloxy.
[0065] The cycloalkyl radicals suitable as substituents are, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
[0066] The cycloalkoxycarbonyl radicals suitable as substituents are, for example, cyclopropoxycarbonyl, cyclobutoxycarbonyl, cyclopentyloxycarbonyl and cyclohexyloxycarbonyl.
[0067] The halocycloalkyl radicals suitable as substituents are, for example, mono-, di- or up to per-halogenated cycloalkyl radicals, for example, fluorocyclopropyl, chlorocyclopropyl, bromocyclopropyl, 2,2-dichlorocyclopropyl, 2,2-difluorocyclopropyl, 2,2-dibromocyclopropyl, 2-fluoro-2-chlorocyclopropyl, 2-chloro-2-bromocyclopropyl, 2,2,3,3-tetrafluorocyclopropyl, 2,2,3,3-tetrachlorocyclopropyl, pentafluorocyclopropyl, fluorocyclobutyl, chlorocyclobutyl, 2,2-difluorocyclobutyl, 2,2,3,3-tetrafluorocyclobutyl, 2,2,3-trifluoro-3-chlorocyclobutyl, 2,2-dichloro-3,3-difluorocyclobutyl, fluorocyclopentyl, difluorocyclopentyl, chlorocyclopentyl, perfluorocyclopentyl, chlorocyclohexyl and pentachlorocyclohexyl.
[0068] Alkylthio is, for example, methylthio, ethylthio, propylthio or butylthio or a branched isomer thereof.
[0069] Phenyl or benzyl per se, or as part of a substituent, such as, for example, phenoxycarbonyl or benzyloxycarbonyl, may be unsubstituted or substituted, in which case the substituents may be in the ortho-, meta- or para-position. Substituents are, for example, C1-C4alkyl, C1-C4alkoxy, halogen or C1-C4haloalkyl.
[0070] Corresponding meanings may also be given to the substituents in combined definitions, such as, for example, in alkyl-S(O)—, alkoxy-N═CH—, (alkyl)2N—C(O)—, (alkyl)2N—N═CH—, alkenyl-NHC(O)—, alkyl(alkenyl)N—C(O)—, alkynyl-NHC(O)—, alkylcarbonyloxyalkyl, alkoxycarbonylalkyl, haloalkoxycarbonyl, haloalkylcarbonyloxyalkyl, haloalkenylcarbonyl, alkyl-S(O)2—NHC(O)—, haloalkyl-S(O)2NHC(O)—, B1-alkoxy and B2-alkyl.
[0071] In the definition of R13, (C1-C5hydroxyalkyl)-CH2—, (B1-C1-C5hydroxyalkyl)-CH2— and (B1-C1-C5-haloalkyl)-CH2— signify that only the C1-C5alkyl moiety is hydroxylated or halogenated, that is to say, the methylene group is not hydroxylated or halogenated.
[0072] In the definition of X1 and R13 together, a group ═N—Y— wherein Y is bonded to the ring nitrogen atom is to be understood as meaning one of the following bicyclic ring systems of formula I: 5
[0073] In the definition of Y, it is always the right-hand end of the bridge member that is bonded to the ring nitrogen atom, as is illustrated, for example where Y is —C(R31)(R32)—CH2—, —C(R31)(R32)—O— and —C(R34)═CH—, in the following bicyclic ring structures: 6
[0074] In the definitions of cyanoalkyl, alkylcarbonyl, alkenylcarbonyl, haloalkenylcarbonyl, alkynylcarbonyl, alkoxycarbonyl, alkylthiocarbonyl and haloalkylcarbonyl, the upper and lower limits of the number of carbon atoms given in each case do not include the cyano or carbonyl carbon atom, as the case may be.
[0075] The compounds of formula I may, in respect of the group W (W1 to W3), be present in the form of mixtures consisting of the isomers substituted in the 3- and 5-positions of the pyrazole ring by the pyridone group (pyridone), for example in the form of regioisomers IW1a and IW1b 7
[0076] for the group W1. The ratio of isomers may vary as a function of the method of synthesis.
[0077] The invention relates also to the salts that the compounds of formula I having azide hydrogen, especially the derivatives having carboxylic acid groups and sulfonamide groups (for example carboxy-substituted alkyl, alkoxy and pyridone groups (R12) and alkyl-S(O)2NH— and haloalkyl-S(O)2NH-13 groups), are capable of forming with bases. Those salts are, for example, alkali metal salts, for example sodium and potassium salts; alkaline earth metal salts, for example calcium and magnesium salts; ammonium salts, that is to say unsubstituted ammonium salts and mono- or poly-substituted ammonium salts, for example triethylammonium and methylammonium salts; or salts with other organic bases.
[0078] Of the alkali metal and alkaline earth metal hydroxides as salt formers, attention is drawn, for example, to the hydroxides of lithium, sodium, potassium, magnesium and calcium, but especially to the hydroxides of sodium and potassium.
[0079] Examples of amines suitable for ammonium salt formation include ammonia as well as primary, secondary and tertiary C1-C18alkylamines, C1-C4hydroxyalkylamines and C2-C4-alkoxyalkylamines, for example methylamine, ethylamine, n-propylamine, isopropylamine, the four isomers of butylamine, n-amylamine, isoamylamine, hexylamine, heptylamine, octylamine, nonylamine, decylamine, pentadecylamine, hexadecylamine, heptadecylamine, octadecylamine, methylethylamine, methylisopropylamine, methylhexylamine, methylnonylamine, methylpentadecylamine, methyloctadecylamine, ethylbutylamine, ethylheptylamine, ethyloctylamine, hexylheptylamine, hexyloctylamine, dimethylamine, diethylamine, di-n-propylamine, diisopropylamine, di-n-butylamine, di-n-amylamine, diisoamylamine, dihexylamine, diheptylamine, dioctylamine, ethanolamine, n-propanolamine, isopropanolamine, N,N-diethanolamine, N-ethylpropanolamine, N-butylethanolamine, allylamine, n-butenyl-2-amine, n-pentenyl-2-amine, 2,3-dimethylbutenyl-2-amine, dibutenyl-2-amine, n-hexenyl-2-amine, propylenediamine, trimethylamine, triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine, triisobutylamine, tri-sec-butylamine, tri-n-amylamine, methoxyethylamine and ethoxyethylamine; heterocyclic amines, for example pyridine, quinoline, isoquinoline, morpholine, thiomorpholine, piperidine, pyrrolidine, indoline, quinuclidine and azepine; primary arylamines, for example anilines, methoxyanilines, ethoxyanilines, o-, m- and p-toluidines, phenylenediamines, benzidines, naphthylamines and o-, m- and p-chloroanilines; especially triethylamine, isopropylamine and diisopropylamine.
[0080] The salts of compounds of formula I having basic groups, especially having basic pyrazolyl rings, or of derivatives having amino groups, for example alkylamino and dialkylamino groups, in the definition of R3, R5 or R13 are, for example, salts with inorganic or organic acids, for example hydrohalic acids, such as hydrofluoric acid, hydrochloric acid, hydrobromic acid or hydriodic acid, and also sulfuric acid, phosphoric acid, nitric acid, and organic acids, such as acetic acid, trifluoroacetic acid, trichloroacetic acid, propionic acid, glycolic acid, thiocyanic acid, citric acid, benzoic acid, oxalic acid, formic acid, benzenesulfonic acid, p-toluenesulfonic acid and methanesulfonic acid.
[0081] The possible presence of at least one asymmetrical carbon atom in the compounds of formula 1, for example in the substituent R13, where R13 is a branched alkyl, alkenyl, haloalkyl or alkoxyalkyl group or where R13 is (B1-C1-C5hydroxyalkyl)-CH2— wherein, for example, B1 is C1-C6alkyl-S(O)—, means that the compounds may occur in the form of optically active single isomers or in the form of racemic mixtures. In the present invention, “compounds of formula I” is to be understood as including both the pure optical antipodes and the racemates or diastereoisomers. When an aliphatic C═C or C═N—O double bond (syn/anti) is present, geometric isomerism may occur. The invention relates to those isomers also.
[0082] Preferred compounds of formula I correspond to formula Ia 8
[0083] R1, R2, R3, R4, R5, R11, R12, R13, X1 and n1 are as defined for formula I. Of the compounds of formula Ia, preference is given to those wherein in the group Wa R3 is C1-C4alkyl or halogen; and R1 is methyl or ethyl.
[0084] Special preference is given to compounds of formula Ia wherein R3 is methyl, halomethyl, chlorine or bromine. Of those, the compounds wherein Wa is a group W1a or W2a are especially important.
[0085] Also especially important are compounds of formula Ia wherein Wa is the group W3a; and R5 is C1- or C2-halomethyl, cyano or H2NC(S)—.
[0086] Also particularly important are compounds of formula Ia wherein Wa is the group W1a; R1 is C1-C4alkyl; R2 is C1- or C2-haloalkyl; R3 is chlorine, bromine, methyl or halomethyl; R11 is fluorine, chlorine or bromine; and R12 is halogen, methyl or halomethyl. Of those, compounds in which R1 is methyl or ethyl; and R2 is difluoromethyl are more especially important.
[0087] Special preference is given also to compounds of formula Ia wherein Wa is the group W2a; R1 is C1-C4alkyl; R4 is methyl or ethyl; R3 is chlorine, bromine or methyl; R11 is fluorine, chlorine or bromine; and R12 is halogen, methyl or halomethyl. Of those compounds, those wherein R1 is methyl or ethyl; and R4 is methyl are more especially preferred.
[0088] Particularly important compounds of formula Ia are those wherein Wa is the group W3a; R1 is C1-C4alkyl; R5 is C1- or C2-haloalkyl, cyano, H2NC(S)— or CH3C(O)—; R3 is chlorine, bromine, methyl or halomethyl; R11 is fluorine, chlorine or bromine; and R12 is halogen, methyl or halomethyl. Of those, especially compounds wherein R1 is methyl or ethyl; and R5 is halomethyl or cyano are more especially important.
[0089] The process according to the invention for the preparation of a compound of formula I 9
[0090] wherein R11, R12 and W are as defined for formula I; X1 is O or S; R13 is C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkyl, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C2-C6haloalkyl, C3-C6haloalkenyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, B1-C1-C6alkyl, 10
[0091] (C1-C5hydroxyalkyl)-CH2—, (B1-C1-C5hydroxyalkyl)-CH2— or (B1-C1-C5haloalkyl)-CH2—; and B1 is as defined for formula I, is carried out analogously to known processes and comprises oxidising a compound of formula III 11
[0092] for example with hydrogen peroxide-urea adduct in the presence of carboxylic acids and/or carboxylic acid anhydrides, organic peracids or persulfonic acid (Caro's acid) in a suitable solvent, to form a compound of formula V 12
[0093] and subsequently rearranging that compound in an inert solvent in the presence of an anhydride or in the presence of antimony pentachloride to yield, after aqueous working up, a compound of formula II 13
[0094] the radicals R11, R12 and W in the compounds of formulae II, III and V being as defined above, and then alkylating that compound in the presence of an inert solvent and a base with a compound of formula VI
R13—L (VI),
[0095] wherein R13 is as defined above and L is a leaving group, preferably chlorine, bromine, iodine, CH3SO2O— or 14
[0096] to form the isomeric compounds of formulae I and IV 15
[0097] wherein R11, R12, R13 and W are as defined above and X1 is O, and subsequently, where appropriate after separating off the compound of formula I, functionalising the pyridone group thereof according to the definition of X1 and R13, if desired, for example, converting it with the aid of a suitable sulfur reagent into the corresponding pyridinethione derivative (X1═S) (Reaction Scheme 1).
[0098] The process according to the invention for the preparation of a compound of formula I 16
[0099] wherein R11, R12 and W are as defined for formula I; X1 is S; R13 is hydroxy, C1-C6alkoxy, C3C6alkenyloxy, C3-C6alkynyloxy, C1-C6haloalkoxy, C3-C6haloalkenyloxy, B1-C1-C6alkoxy, C1-C6alkylcarbonyl, C1-C6alkylcarbonyloxy, C1-C6haloalkylcarbonyl, C2-C6alkenylcarbonyl or C1-C6alkoxycarbonyl; and B1 is as defined for formula I, is carried out analogously to known processes and comprises first of all oxidising a compound of formula III 17
[0100] to yield a compound of formula V 18
[0101] chlorinating or brominating that compound to form a compound of formula VIII 19
[0102] the radicals R11, R12 and W in the compounds of formulae III, V and VIII being as defined above and Hal in the compound of formula VIII being chlorine or bromine, subsequently converting the compound of formula VIII with a suitable sulfur reagent, for example thiourea, sodium hydrogen sulfide (NaSH) or phosphorus pentasulfide (P2S5), in the presence of a solvent into a compound of formula Ic 20
[0103] and reacting that compound in the presence of a solvent and a base with a compound of formula XI
R14—L (XI),
[0104] wherein R14 is C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C3-C6haloalkenyl, B1-C1-C6alkyl or C1-C6alkylcarbonyl; B1 is as defined above; and L is a leaving group (Reaction Scheme 2).
[0105] The process according to the invention for the preparation of a compound of formula I 21
[0106] wherein R11, R12, R13 and W are as defined for formula I and X1 is S is carried out analogously to known processes and comprises treating a compound of formula I 22
[0107] wherein R11, R12, R13 and W are as defined above and X1 is O, with a sulfur reagent in an inert solvent.
[0108] The preparation of compounds of formula I wherein X1 is O or S; and R13 is C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkyl, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C2-C6haloalkyl, C3-C6haloalkenyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, B1-C1-C6alkyl, 23
[0109] (C1-C5hydroxyalkyl)-CH2—, (B1-C1-C5hydroxyalkyl)-CH2— or (B1-C1-C5haloalkyl)-CH2—; and B1 is as defined for formula I is illustrated in the following Reaction Scheme 1. 24
[0110] The pyridine N-oxides of formula V (Reaction Scheme 1) can be prepared according to known methods (e.g. Org. Synth. 4, 828 (1963); ibid. 3, 619 (1955); U.S. Pat. No. 3,047,579; and B. Iddon and H. Suschitzky in “Polychloroaromatic Compounds”, Editor H. Suschitzky, Plenum Press, London 1974, page 197), advantageously by reaction of a pyridine derivative of formula III with an oxidising agent, such as, for example, an organic peracid, for example m-chloroperbenzoic acid (MCPBA), peracetic acid or pertrifluoroacetic acid, or aqueous hydrogen peroxide solution or hydrogen peroxide-urea adduct together with a carboxylic acid and/or a carboxylic acid anhydride, or an inorganic peracid, for example pertungstic acid. Solvents suitable for that reaction are, for example, water, organic acids, for example acetic acid and trifluoroacetic acid, halogenated hydrocarbons, for example dichloromethane and 1,2-dichloroethane, esters, for example ethyl acetate, ethers, for example tetrahydrofuran and dioxane, or mixtures of those solvents. The reaction temperatures are generally in the range from −20° C. to 100° C., depending on the solvent or mixture of solvents used.
[0111] The 6-hydroxypyridine derivatives of formula II can be prepared according to known methods (e.g. Quart. Rev. 10, 395 (1956); J. Am. Chem. Soc. 85, 958 (1963); and J. Org. Chem. 26, 428 (1961)), advantageously by rearrangement of the pyridine N-oxides of formula V in the presence of an anhydride, for example acetic anhydride, trifluoroacetic anhydride or methanesulfonic anhydride, in a suitable inert solvent, such as, for example, a halogenated hydrocarbon, for example dichloromethane or 1,2-dichloroethane, an amide, for example N,N-dimethylformamide or 1-methyl-2-pyrrolidone (NMP), and, where appropriate, in the presence of sodium acetate. The reaction temperatures are generally in the range from −30° C. to 80° C.
[0112] The 6-O-acyl- or 6-O-sulfonyl-pyridines formed first can readily be hydrolysed, by aqueous working up of the reaction mixture, to form the desired 6-hydroxypyridines of formula II. Analogously to Tetrahedron 37, 187 (1981), as a further variant it is possible to use antimony pentachloride in the above rearrangement reaction.
[0113] The subsequent alkylation may be carried out according to known methods (e.g. Org. Prep. Proced. Int. 9, 5 (1977); J. Org. Chem. 35, 2517 (1970); ibid. 32, 4040 (1967); and Tetrahedron Lett. 36, 8917 (1995) as well as Preparation Examples P20 and P21), advantageously using an alkylation reagent of formula VI. The alkylation usually results in an isomeric mixture consisting of the compounds of formulae I (N-alkylation) and IV (O-alkylation).
[0114] Suitable solvents are, for example, alcohols, for example methanol, ethanol and isopropanol, amides, for example N,N-dimethylformamide (DMF) and 1-methyl-2-pyrrolidone (NMP), sulfoxides, for example dimethyl sulfoxide (DMSO), and sulfones, for example sulfolan, or mixtures of the above solvents with water, ethers, for example diethyl ether, tert-butyl methyl ether, dimethoxyethane (DME), dioxane and tetrahydrofuran (THF), esters, for example ethyl acetate, ketones, for example acetone and methyl ethyl ketone, and hydrocarbons, for example n-hexane, toluene and xylenes.
[0115] Suitable bases are organic and inorganic bases, for example alkali metal alcoholates, for example sodium methanolate, sodium ethanolate and potassium tert-butanolate, trialkylammonium hydroxides, trialkylammonium halides, for example triethylammonium iodide, alkali metal and alkaline earth metal hydrides, for example sodium hydride together with lithium bromide (2 equivalents), alkali metal carbonates, for example potassium carbonate, alkali metal hydroxides, for example sodium and potassium hydroxide, and also caesium fluoride.
[0116] The reaction temperatures for the alkylation are in the range from −20° C. to the reflux temperature of the solvent used, preferably from 0° C. to 50° C.
[0117] The isomers of formulae I and IV can readily be separated by means of silica gel chromatography or fractional crystallisation.
[0118] Optionally, the desired pyridone derivative of formula I separated from the secondary product of formula IV can readily be converted into the corresponding pyridinethione derivative (X1═S) according to known methods (e.g. Bull. Soc. Chim. Fr. 1953, 1001; and J. Am. Chem. Soc. 73, 3681 (1951)), for example with the aid of a suitable sulfur reagent, for example Lawesson's reagent or phosphorus pentasulfide in an inert solvent, such as, for example, a xylene, pyridine or sulfolan. The reaction temperatures are generally in the range from 20° C. to the boiling temperature of the solvent used.
[0119] The preparation of compounds of formula I wherein X1 is S; and R13 is hydroxy, C1-C6alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6haloalkoxy, C3-C6haloalkenyloxy, B1-C1-C6alkoxy, C1-C6alkylcarbonyl, C1-C6alkylcarbonyloxy, C1-C6haloalkylcarbonyl, C2-C6alkenylcarbonyl or C1-C6alkoxycarbonyl; and B1 is as defined for formula I is illustrated in the following Reaction Scheme 2. 25
[0120] The procedure for the preparation of pyridine N-oxides of formula V (Reaction Scheme 2) is analogous to that indicated under Reaction Scheme 1.
[0121] The pyridine N-oxides of formula V can be converted into the corresponding 6-chloro- or 6-bromo-pyridine derivatives of formula VIII analogously to known processes (e.g. Heterocycles 30, 875 (1990); Can. J. Chem. 31, 457 (1953); and J. Org. Chem. 19, 1633 (1954)), advantageously using a halogenating agent, for example phosphorus oxychloride, phosphorus oxybromide, sulfuryl chloride, thionyl chloride or phosphorus pentachioride in phosphorus oxychloride. The halogenation can generally be carried out at temperatures of from 20° C. to 100° C.
[0122] The reaction of the halopyridine N-oxides of formula VIII to form the compound of formula Ic can be effected analogously to known processes (e.g. U.S. Pat. Nos. 2,742,476, 2,809,971, J. Am. Chem. Soc. 72, 4362 (1950) and J. Chem. Soc. 1939, 1858), advantageously using a suitable sulfur reagent, such as, for example, hydrogen sulfide, sodium hydrogen sulfide or thiourea, in a solvent, such as, for example, water, an alcohol, for example ethanol, or a water/alcohol mixture, or an amide, for example N,N-dimethylformamide (DMF) or NMP. The reaction is generally carried out at temperatures of from −10° C. to 100° C.
[0123] The reaction of the compound of formula Ic with the reactive reagent of formula XI, wherein L is a leaving group, such as, for example, halogen, for example chlorine, bromine or iodine, CH3SO2O—, 26
[0124] or, in the case where R14 is C1-C6alkylcarbonyl and there is used as reactive reagent of formula XI the corresponding acid anhydride, C1-C6alkylcarbonyloxy, can be carried out analogously to known processes (e.g. Tetrahedron Lett. 31, 1965 (1990); Tetrahedron 1991, 7091; and J. Org. Chem. 54, 4330 (1989)). Advantageously, equimolar amounts of compound of formula Ic and reactive reagent of formula XI are reacted at temperatures of from 0° C. to 100° C. in the presence of a solvent and a base.
[0125] Suitable solvents include the familiar inert organic solvents, such as, for example, chlorinated hydrocarbons, for example dichloromethane, aromatic hydrocarbons, for example benzene, toluene and pyridine, ethers, for example dioxane and DME, amides, for example N,N-dimethylformamide and NMP, and sulfoxides, for example DMSO. Suitable bases include the known inorganic and organic bases, such as, for example, alkali metal and trialkylammonium hydroxides, for example sodium or potassium hydroxide and triethylammonium hydroxide, respectively, carbonates, for example sodium and potassium carbonate, and alcoholates, for example sodium ethanolate or potassium isopropanolate. The reaction may also, where appropriate, be carried out under phase transfer conditions. There may be used as phase transfer catalysts the customary quaternary ammonium salts, such as, for example tetraoctylammonium bromide and benzyltriethylammonium chloride. Under those conditions, a suitable organic solvent is any inert non-polar solvent, such as, for example, benzene or toluene.
[0126] The preparation of compounds of formula I wherein X1 is S; and R13 is C1-C6alkoxy-C1-C6-alkyl, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkyl, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C2-C6haloalkyl, C3-C6haloalkenyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, B1-C1-C6alkyl, 27
[0127] (C1-C5hydroxyalkyl)-CH2—, (B1-C1-C5hydroxyalkyl)-CH2— or (B1-C1-C5haloalkyl)-CH2—; and B1 is as defined for formula I is illustrated in the following Reaction Scheme 3. 28
[0128] The conversion of the pyridone derivatives of formula I wherein R11, R12, R13 and W are as defined for formula I and X1 is O into the corresponding pyridinethione derivatives of formula I wherein X1 is S (Reaction Scheme 3) can be carried out analogously to known processes (e.g. J. Het. Chem. 25, 511 (1988); ibid. 22, 265 (1985); Bull. Soc. Chim. Fr. 1953, 1001; J. Prakt. Chem. 1988, 293; Chem. Ber. 62, 2732 (1929); Chem. Heterocycl. Compd. (Engl. Transl.) 1988, 658; Pharmazie 45, 731 (1990); and J. Prakt. Chem./Chem-Ztg 334, 119 (1992)), advantageously with the aid of a sulfur reagent such as, for example, P2S5 or Lawesson's reagent, in an organic solvent, such as, for example, an aromatic hydrocarbon, for example benzene, toluene, a xylene or pyridine, a halogenated aromatic hydrocarbon, for example dichlorobenzene, or an amide, for example DMF or NMP. The reaction temperatures are generally in the range from 20° C. to 200° C. depending on the solvent used.
[0129] The compounds lying within the scope of formula I wherein X1 and R13 together form a group ═N—Y— and Y is, for example, a bridge member —C(R31)(R32)—CH2— can be prepared analogously to known processes, as described, for example, in Sov. Prog. Chem. (Engl. Transl.) 42, 65 (1976); J. Chem. Soc., Perkin Trans 1 1976, 201; Justus Liebigs Ann. 1978, 1491; and Helv. Chim. Acta 73,1679 (1990).
[0130] The compounds lying within the scope of formula I wherein X1 and R13 together form a group ═N—Y— and Y is, for example, a bridge member —C(R34)═CH— can be prepared analogously to known processes, as described, for example, in Farmaco Ed. Sci. 37, 22 (1982); J. Chem. Res. (Miniprint) II, 3368 (1986); and J. Chem. Soc., Perkin Trans 1 1987, 1159.
[0131] Taking into consideration the chemical properties of the pyridyl or pyridonyl moiety, as the case may be, all other compounds within the scope of formula I can readily be prepared, in terms of the construction of the pyrazole rings, in a manner analogous to that described in Preparation Examples P1 to P21, or as described, for example, in “Methoden der Organ-ischen Chemie” (Houben-Weyl), Volume E 8b, Georg Thieme Verlag Stuttgart, 1994, page 399 ff.; or in “Pyrazoles, Pyrazolines, Pyrazolidines, Indazoles and Condensed Rings”, Editor R. H. Wiley, Interscience Publishers, John Wiley & Sons, New York, 1967, page 1 ff.; or as described in the patent specifications WO 96/01254 and WO 97/00246.
[0132] A large number of known standard processes are available for the preparation of the pyridine derivatives of formula III, the choice of a suitable process being governed by the properties (reactivities) of the substituents in the respective intermediates. A number of specimen examples are also given in Preparation Examples P1 to P16. For example, a compound of formula III 29
[0133] wherein W is a group 30
[0134] (W1); R1, R2, R11 and R12 are as defined for formula I; and R3 is hydrogen, halogen, C1-C4alkyl or C1-C4haloalkyl, can be prepared starting from, for example, a compound of formula XII 31
[0135] wherein R11 and R12 are as defined above, which is reacted in an alcohol of formula XIII
R8—OH (XIII),
[0136] wherein R8 is C1-C4alkyl, in the presence of a suitable palladium or nickel catalyst, such as, for example, palladium bis(triphenylphosphine) dichloride (PdCl2(PPh3)2) and a base, such as, for example, triethylamine, under carbon monoxide excess pressure, to form a compound of formula XIV 32
[0137] wherein R8, R11 and R12 are as defined above, which is subjected to acid or basic hydrolysis to form the corresponding carboxylic acid of formula XV 33
[0138] and converted with a carboxylic acid halogenating reagent, such as, for example, thionyl chloride, phosphorus pentachloride or oxalyl chloride, into the corresponding carboxylic acid halide of formula XVI 34
[0139] wherein R11 and R12 are as defined above and X2 is halogen, preferably chlorine, and that compound is reacted in a solvent, such as, for example, acetonitrile in the presence of an alkaline earth metal salt, preferably magnesium chloride, and a base, such as, for example, triethylamine, with the malonic acid mono ester · salt of formula XVII 35
[0140] wherein R3 is hydrogen, C1-C4alkyl or C1-C4haloalkyl; M1+ is an alkali metal ion, preferably a potassium ion; and R7 is C1-C4alkoxy, to yield the keto ester of formula XIX 36
[0141] wherein R3, R7, R11 and R12 are as defined above, and that compound is cyclised in a solvent, such as, for example, glacial acetic acid, with a compound of formula XX
NH2NH—R1 (XX),
[0142] wherein R1 is as defined for formula I, to yield a compound of formula XXI 37
[0143] wherein R1, R3, R11 and R12 are as defined above, and subsequently in accordance with standard methods the hydroxyl group is functionalised, especially freonised (Example P13), according to the definition of R2, and the pyrazole ring is optionally halogenated (R3 is halogen; Example P14) or oxidised to the corresponding pyridine N-oxide (Example P17). The compounds of formula XXII 38
[0144] wherein R1, R3, R5, R11 and R12 are as defined for formula I, are important intermediates for the preparation of compounds of formula III, especially compounds of formula III wherein W is a group W3; R5 is haloalkyl (Example P11); and R1, R3, R11 and R12 are as defined for formula I.
[0145] The compounds of formula XXII are prepared according to EP-A-0 361 114, U.S. Pat. No. 5,032,165, WO 92/02509, WO 92/06962, WO 95/33728 and WO 96/01254.
[0146] The compounds of formula XIX 39
[0147] wherein R11 and R12 are as defined for formula I; R3 is hydrogen, C1-C4alkyl or C1-C4-haloalkyl; and R7 is C1-C4alkoxy, C1- or C2-haloalkyl or C1-C4alkoxycarbonyl, are important intermediates for the preparation of compounds of formula I, especially compounds of formula I wherein W is a group 40
[0148] (W1); R1, R2, R11 and R12 are as defined for formula I; and R3 is hydrogen, halogen, C1-C4alkyl or C1-C4haloalkyl. The compounds of formula XXIII 41
[0149] wherein R11 and R12 are as defined for formula I; and R3 is hydrogen, halogen, C1-C4alkyl or C1-C4haloalkyl, are important intermediates for the preparation of compounds of formula Ia wherein Wa is a group W3a; R5 is hydrogen; and R1, R3, R11 and R12 are as defined for formula I (Example 8).
[0150] The compounds of formula XXIII are prepared according to EP-A-0 361 114, U.S. Pat. No. 5,032,165, WO 92/02509, WO 92106962, WO 95/33728 and WO 96/01254.
[0151] The compounds of formula XXIV 42
[0152] wherein R11 and R12 are as defined for formula I; and R3 is hydrogen, C1-C4alkyl or C1-C4-haloalkyl, are important intermediates for the preparation of compounds of formula I wherein W is a group W3 43
[0153] W3); R3 is hydrogen, C1-C4alkyl or C1-C4haloalkyl; R5 is amino; and R1, R11 and R12 are as defined for formula I.
[0154] The compounds of formula XXIV are prepared according to EP-A-0 361 114, U.S. Pat. No. 5,032,165, WO 92/02509, WO 92/06962, WO 95/33728 and WO 96/01254.
[0155] A large number of known standard processes are available for the preparation of the pyridonylpyrazoles of formula I substituted at the pyridone ring, the choice of a suitable preparation process being governed by the properties (reactivities) of the substituents in the respective intermediates.
[0156] A number of specimen examples are also given in Preparation Examples P19 to P24. The compound of formula XII, and the starting compounds 2,5dichloro-3-fluoropyridine, 2,3-dichloro-5-trifluoromethylpyridine and 3,5-dichloro-2-acetylpyridine used in Preparation Examples P1, P2 and P9, are either known or can be prepared analogously to published processes.
[0157] The reagents of formulae VI and XI used in the Reaction Schemes 1, 2 and 3 are either known or can be prepared analogously to published processes.
[0158] All other compounds within the scope of formula I can readily be prepared, taking into consideration the respective chemical reactivities, analogously to the processes according to Preparation Examples P1 to P25, or analogously to the methods described in “Methoden der Organischen Chemie” (Houben-Weyl), volume E 8b, Georg Thieme Verlag Stuttgart, 1994, page 399 ff.; ibid, volume E7B, Georg Thieme Verlag Stuttgart, 1992, page 286 ff.; in “Pyrazoles, Pyrazolines, Pyrazolidines, Indazoles and Condensed Rings”, Editor R. H. Wiley, Interscience Publishers, John Wiley & Sons, New York, 1967, page 1 ff.; or in “Comprehensive Heterocyclic Chemistry”, Editors A. R. Katritzky and C. W. Rees, Pergamon Press, Oxford, 1987, or by derivatisation according to known standard methods as described, for example, in “Advanced Organic Chemistry, Third Edition, Editor J. March, John Wiley & Sons, New York, 1985; in “Comprehensive Organic Transformations”, Editor R. C. Larock, VCH Publishers, Inc., New York, 1989; or in “Comprehensive Organic Functional Group Transformations”, Editors A. R. Katritzky, O. Meth-Cohn, C. W. Rees, Pergamon Press, Oxford, 1995, or as described in the Patent Specifications EP-A-0 361 114, U.S. Pat. No. 5,032,165, WO 92/02509, WO 92/06962, WO 95/33728 and WO 96/01254.
[0159] The end products of formula I can be isolated in conventional manner by concentration or evaporation of the solvent and purified by recrystallisation or trituration of the solid residue in solvents in which they are not readily soluble, such as ethers, aromatic hydrocarbons or chlorinated hydrocarbons, by distillation or by means of column chromatography and a suitable eluant. The sequence in which it is advantageous for certain reactions to be carried out so as to avoid possible secondary reactions will also be familiar to the person skilled in the art. Unless the synthesis is specifically aimed at the isolation of pure isomers, the product may be obtained in the form of a mixture of two or more isomers. The isomers can be separated according to methods known per se.
[0160] For the use according to the invention of the compounds of formula I or of compositions comprising them, there come into consideration all methods of application customary in agriculture, for example pre-emergence application, post-emergence application and seed dressing, and also various methods and techniques such as, for example, the controlled release of active ingredient. For that purpose a solution of the active ingredient is applied to mineral granule carriers or polymerised granules (urea/formaldehyde) and dried. If required, it is also possible to apply a coating (coated granules), which allows the active ingredient to be released in metered amounts over a specific period of time.
[0161] The compounds of formula I may be used in unmodified form, that is to say as obtained in the synthesising process, but they are preferably formulated in customary manner together with the adjuvants conventionally employed in formulation technology, for example into emulsifiable concentrates, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granules or microcapsules. Such formulations are described, for example, in WO 97/34485, pages 9 to 13. As with the nature of the compositions, the methods of application, such as spraying, atomising, dusting, wetting, scattering or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances.
[0162] The formulations, that is to say the compositions, preparations or mixtures comprising the compound (active ingredient) of formula I or at least one compound of formula I and, usually, one or more solid or liquid formulation adjuvants, are prepared in known manner, e.g. by homogeneously mixing and/or grinding the active ingredients with the formulation adjuvants, for example solvents or solid carriers. Surface-active compounds (surfactants) may also be used in addition in the preparation of the formulations. Examples of solvents and solid carriers are given, for example, in WO 97/34485, page 6.
[0163] Depending on the nature of the compound of formula I to be formulated, suitable surface-active compounds are non-ionic, cationic and/or anionic surfactants and surfactant mixtures having good emulsifying, dispersing and wetting properties. Examples of suitable anionic, non-ionic and cationic surfactants are listed, for example, in WO 97/34485, pages 7 and 8.
[0164] In addition, the surfactants conventionally employed in formulation technology, which are described in, inter alia, “McCutcheon's Detergents and Emulsifiers Annual” MC Publishing Corp., Ridgewood N.J., 1981, Stache, H., “Tensid-Taschenbuch”, Carl Hanser Verlag, Munich/Vienna 1981, and M. and J. Ash, “Encyclopedia of Surfactants”, Vol. I-III, Chemical Publishing Co., New York, 1980-81, are also suitable for the preparation of the herbicidal compositions according to the invention.
[0165] The herbicidal formulations generally contain from 0.1 to 99% by weight, especially from 0.1 to 95% by weight, of herbicide, from 1 to 99.9% by weight, especially from 5 to 99.8% by weight, of a solid or liquid formulation adjuvant, and from 0 to 25% by weight, especially from 0.1 to 25% by weight, of a surfactant. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations. The compositions may also comprise further ingredients, such as stabilisers, for example vegetable oils or epoxidised vegetable oils (epoxidised coconut oil, rape oil or soybean oil), anti-foams, for example silicone oil, preservatives, viscosity regulators, binders, tackifiers, and also fertilisers or other active ingredients.
[0166] The compounds of formula I can be used successfully either in the form of a mixture comprising the isomers IW1a and IW1b or in the form of pure isomer IW1a or IW1b, generally on plants or the locus thereof, at rates of application of from 0.001 to 4 kg/ha, especially from 0.005 to 2 kg/ha. The concentration required to achieve the desired effect can be determined by experiment. It is dependent on the nature of the action, the stage of development of the cultivated plant and of the weed and on the application (place, time, method) and may vary within wide limits as a function of those parameters.
[0167] The compounds of formula I and, generally, the isomers of formula Ia especially, are distinguished by herbicidal and growth-inhibiting properties, allowing them to be used in crops of useful plants, especially cereals, cotton, soybeans, sugar beet, sugar cane, plantation crops, rape, maize and rice, and also for non-selective weed control.
[0168] “Crops” is to be understood as meaning also crops that have been made tolerant to herbicides or classes of herbicides as a result of conventional methods of breeding or genetic techniques. The weeds to be controlled may be either monocotyledonous or dicotyledonous weeds, such as, for example, Stellaria, Nasturtium, Agrostis, Digitaria, Avena, Setaria, Sinapis, Lolium, Solanum, Phaseolus, Echinochloa, Scirpus, Monochoria, Sagittaria, Bromus, Alopecurus, Sorghum halepense, Rottboellia, Cyperus, Abutilon, Sida, Xanthium, Amaranthus, Chenopodium, Ipomoea, Chrysanthemum, Galium, Viola and Veronica.
[0169] The following Examples further illustrate but do not limit the invention.
PREPARATION EXAMPLES Example P1:3-Fluoro-5-chloro-2-pyridinecarboxylic acid ethyl ester[0170] 44
[0171] An autoclave is charged with 31.4 g of 2,5-dichloro-3-fluoropyridine, 400 ml of dry ethanol, 27.8 ml of triethylamine and 3.5 g of palladium bis(triphenylphosphine) dichloride (PdCl2(PPh3)2) and then a pressure of 180 bars is applied with carbon monoxide. The mixture is maintained at 90° C. for 4 days. After cooling and releasing the pressure, a further 3.5 g of PdCl2(PPh3)2 are added, a pressure of 130 bars is applied with carbon monoxide, and the mixture is maintained at 90° C. for 3 days, after which it is cooled to 25° C., the pressure is released and the mixture is discharged. After concentration in vacuo, absorption from ethyl acetate onto silica gel is carried out. The silica gel is applied to a flash chromatography column (silica gel) and then eluted with n-hexane/ethyl acetate 3/1. 24.3 g of the desired target compound having a melting point of 48-50° C. are obtained.
Example P2: 3-Chloro-5-trifluoromethyl-2-pyridinecarboxylic acid ethyl ester[0172] 45
[0173] An autoclave is charged with 200 g of 2,3-dichloro-5-trifluoromethylpyridine, 1.85 liters of ethanol, 260 ml of triethylamine and 6.5 g of palladium bis(triphenylphosphine) dichloride (PdCl2(PPh3)2). At 25° C. a pressure of 110 bars is then applied with carbon monoxide and the mixture is maintained at 110° C. for 24 hours. After cooling to 25° C., the crude mixture is concentrated to a thick slurry, which is then partitioned between dilute sodium chloride solution and ethyl acetate. After extraction by shaking, and separation of the phases, the ethyl acetate phase is washed with water, dried over sodium sulfate and concentrated to dryness. The crude product is distilled under a high vacuum of 0.035 mbar. 200 g of the desired product are obtained in the form of a yellow oil having a boiling point of 67-70° C./0.035 mbar (yield 85% of the theoretical yield).
Example P3: 3-Chloro-5-trifluoromethyl-2-pyridinecarboxylic acid[0174] 46
[0175] 423 g of 3-chloro-5-trifluoromethyl-2-pyridinecarboxylic acid ethyl ester (Example P2) is placed in a mixture of 800 ml of water and 160 ml of ethanol. 800 ml of a 2N sodium hydroxide solution are added dropwise at below 35° C. After 3 hours, the mixture is washed twice with dichloromethane and then rendered acidic with excess concentrated hydrochloric acid while cooling with an ice-bath. The resulting slurry is filtered, washed with water and dried in vacuo. 318 g of the desired product are obtained in the form of a white solid having a melting point of 135° C. (decomposition).
Example P4: 3-Fluoro-5-chloropyridine-2-carboxylic acid[0176] 47
[0177] 70 g of 3-fluoro-5-chloro-2-pyridinecarboxylic acid ethyl ester (Example P1) are placed in 105 ml of dimethyl sulfoxide (DMSO). 230 ml of a 2N sodium hydroxide solution are added dropwise at 40° C. over a period of 30 minutes. The resulting yellow suspension is introduced into a mixture of 2 liters of ice-water and 400 ml of 2N hydrochloric acid. After subsequently stirring for 20 minutes, the mixture is filtered and the filtration residue is washed twice with water. 56.4 g of the desired target compound are obtained in the form of a white solid.
[0178] 1H-NMR (DMSO-D6): 13.79 ppm (broad signal, 1H); 8.60 ppm (d, 1H); 8.27 ppm (dxd, 1H).
Example P5: 3-Chloro-5-trifluoromethyl-2-pyridinecarboxylic acid chloride[0179] 48
[0180] 89.3 g of 3-chloro-5-trifluoromethyl-2-pyridinecarboxylic acid (Example P3) are slowly heated to reflux with 60 ml of thionyl chloride and the mixture is then stirred at that temperature for 4 hours, after which it is cooled to 25° C. and concentrated to dryness in vacuo. Twice, toluene is added and the mixture is again concentrated to dryness. 94.0 g of the desired product are obtained in the form of a yellow residue.
[0181] 1H-NMR (CDCl3): 8.91 ppm (d, 1H); 8.13 ppm (d, 1H).
Example P6: 3-Fluoro-5-chloro-2-pyridinecarboxylic acid chloride[0182] 49
[0183] 71.38 g of 3-fluoro-5-chloro-2-pyridinecarboxylic acid (Example P4) are placed in a round-bottomed flask and heated to 90° C. 59 ml of thionyl chloride are added dropwise from a dropping funnel over a period of 30 minutes, and the gas formed is introduced into sodium hydroxide solution. Stirring is then carried out for 5 hours at 100° C., after which the thionyl chloride is distilled off at normal pressure. After the addition of 50 ml of dry toluene, 20 ml thereof are distilled off. The resulting solution is poured into 200 ml of n-hexane and stirred overnight. After cooling in an ice-bath, the mixture is filtered and the filtration residue is washed twice with n-hexane. 68.7 g of the desired compound are obtained in the form of a brown solid.
[0184] 1H-NMR (CDCl3): 8.60 ppm (d, 1H); 7.69 ppm (dxd, 1H).
Example P7: 5-Chloro-3-fluoro-2-pyridinecarbaldehyde[0185] 50
[0186] 110 g of 5-chloro-3-fluoro-2-pyridinecarboxylic acid ethyl ester (Example P1) are dissolved in 180 ml of tert-butanol. 27.4 g of sodium borohydride (NaBH4, 97%) are added to the slightly brown solution, in the course of which a weak exothermic reaction is observed. By cooling occasionally with an ice-bath, the internal temperature is maintained below 30° C. The exothermic reaction has subsided after 1½ hours. The reaction mixture is then stirred overnight at 22° C. and subsequently cold water is added slowly, while stirring well. Extraction is carried out with diethyl ether, and the combined ethereal phases are washed with dilute sodium hydrogen carbonate solution and brine, dried over sodium sulfate, filtered and concentrated in vacuo. 58 g of a tacky solid are isolated. After digestion with n-hexane/diethyl ether 50/1 and drying in vacuo, 48.6 g of a yellow solid are obtained having an Rf value on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 1/1 (v/v)) of 0.40.
[0187] 160.7 g of active manganese(IV) oxide (90%) are added to 22.4 g of the alcohol obtained as intermediate in 300 ml of methylene chloride, and a slight exothermic reaction can be detected. After stirring for 3 hours, the mixture is filtered over Hyflo and the filtrate is concentrated in vacuo. The residue (20 g) is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 4/1 (v/v)). In that manner 11.0 g of the desired target compound are obtained in the form of a white solid having a melting point of 70-72° C. The Rf value of the product on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 3/1 (v/v)) is 0.61.
Example P8: 3-Chloro-5-trifluoromethyl-2-acetylpyridine[0188] 51
[0189] 55.3 ml of malonic acid dimethyl ester are stirred with 129 ml of triethylamine and 24.9 g of anhydrous magnesium chloride for 2 hours in 250 ml of dry toluene. With the exothermic reaction, the reaction temperature rises to 45° C. At 25° C. 94.0 g of 3-chloro-5-trifluoromethyl-2-pyridinecarboxylic acid chloride (Example P5) in 150 ml of toluene are added dropwise thereto and the reaction mixture is further stirred overnight. An excess of concentrated hydrochloric acid is then added dropwise, and the mixture is diluted with water and extracted with ethyl acetate. The organic phase is washed with brine, dried over sodium sulfate, filtered and concentrated to yield 142 g of a red oil which is slowly introduced into a mixture of 20 ml of water and 400 ml of dimethyl sulfoxide, which is under gentle reflux by means of an oil bath of a temperature of 150° C. When the evolution of gas can no longer be detected, water is added and extraction is carried out with ether. The combined ethereal phases are washed with water, dried over sodium sulfate, filtered and concentrated. The residue is purified by means of column chromatography (silica gel; eluant: n-hexane/ethyl acetate 15/1 (v/v)), yielding 61 g of the desired product in the form of a yellow oil (70% of the theoretical yield).
[0190] 1H-NMR (CDCl3): 8.81 ppm (d, 1H); 8.05 ppm (d, 1H); 2.72 ppm (s, 3H).
Example P9: 1-(3-Chloro-5-trifluoromethyl-2-pyridyl)-3-dimethylamino-2-propen-1-one[0191] 52
[0192] 5.0 g of 3-chloro-5-trifluoromethyl-2-acetylpyridine (Example P8) are introduced into 30 ml of toluene and 3.60 ml of N,N-dimethylformamide-dimethylacetal are added. The resulting yellow solution is stirred overnight at 100° C. After cooling to 25° C., the mixture is concentrated to dryness in vacuo, yielding 6.17 g of the desired target compound in the form of a dark-yellow oil which later solidifies.
[0193] 1H-NMR (CDCl3): 8.74 ppm (d, 1H); 7.98 ppm (d, 1H); 7.92 ppm (broad signal, 1H); 5.54 ppm (broad d, 1H); 3.17 ppm (broad signal, 3H); 2.94 ppm (broad signal, 3H).
Example P10: 3-(3.5-Dichloro-2-pyridyl)-5-trifluoromethyl-[1H]-pyrazole[0194] 53
[0195] 15.8 g of 3,5-dichloro-2-acetylpyridine are introduced together with 12.0 ml of trifluoroethyl acetate into 125 ml of absolute ether. With stirring, the mixture is cooled using an ice-bath and 46.6 ml of a 21% sodium ethanolate solution in ethanol are added dropwise. The ice-bath is then removed and the mixture is subsequently stirred overnight at 25° C. After cooling the reaction mixture in an ice-bath and adding dropwise 7.5 ml of glacial acetic acid, the mixture is concentrated in vacuo. 39.0 g of 1-(3,5-dichloro-2-pyridyl)-3-trifluoromethyl-propane-3-dione are obtained, which can be used directly for the following cyclisation step.
[0196] 39.0 g of 1-(3,5-dichloro-2-pyridyl)-3-trifluoromethylpropane-1,3-dione 54
[0197] are introduced into ethanol and 4.85 ml of hydrazine hydrate are slowly added. The reaction mixture is then heated at reflux with stirring. After one hour, the mixture is concentrated to dryness in vacuo and the residue is partitioned between dilute sodium hydrogen carbonate solution and ethyl acetate. After extraction by shaking, and separation of the phases, the organic phase is washed with brine, dried over sodium sulfate, filtered and concentrated to dryness. 22.25 g of a yellow oil are obtained, which is purified by means of flash chromatgraphy (silica gel; eluant: n-hexane/ethyl acetate 4/1 (v/v)) to yield 15.0 g of the desired product in the form of a yellow solid.
[0198] 1H-NMR (DMSO-D6): 8.81 ppm (m, 1H); 8.64 ppm (m, 1H); 8.26 ppm (m, 1H); 7.45 ppm (broad signal, 1H).
Example P11: 3-(3,5-Dichloro-2-pyridyl)-5-trifluoromethyl-1-methyl-[1H]-pyrazole and 5-(3,5-dichloro-2-pyridyl)-3-trifluoromethyl-1-methyl-[1H]-pyrazole[0199] 55
[0200] 8.88 g of 3-(3,5-dichloro-2-pyridyl)-5-trifluoromethyl-[1H]-pyrazole (Example P10) are introduced into 35 ml of N-methylpyrrolidone. After the addition of 13.0 g of potassium carbonate, the mixture is stirred and heated to 55° C. 2.36 ml of methyl iodide in 5.0 ml of N-methylpyrrolidone are then slowly added dropwise. After subsequently stirring for 2 hours, diethyl ether and water are added, the mixture is extracted by shaking and the organic phase is separated off. The separated ethereal phase is washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product is purified by means of flash chromatography (silica gel; eluant: toluene/ethyl acetate 100/1). First of all 3.96 g of the 5-pyridylpyrazole isomer (yield 42%) are isolated in the form of a yellow oil and then 1.96 g of the 3-pyridylpyrazole (yield 21%) are isolated in the form of a yellow solid. The Rf values of the 3- and 5-pyridylpyrazole isomers on silica gel 60 F254 using toluene/ethyl acetate 30/1 as eluant (UV) are:
[0201] Rf value of 5-pyridylpyrazole: 0.50
[0202] Rf value of 3-pyridylpyrazole: 0.35
Example P12: 3-(3,5-Dichloro-2-pyridyl)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole[0203] 56
[0204] 2.0 g of 3-(3,5-dichloro-2-pyridyl)-5-trifluoromethyl-1-methyl-[1H]-pyrazole (Example P11) are introduced into glacial acetic acid at 40° C. and, with stirring, chlorine gas is slowly passed over the solution. The reaction can be monitored analytically by means of thin-layer chromatography (silica gel 60 F254, eluant: n-hexane/ethyl acetate 4/1, UV). Once starting material can no longer be detected, glacial acetic acid is removed in vacuo and the residue is partitioned between dilute aqueous sodium hydroxide solution and ethyl acetate. After extraction by shaking, the separated organic phase is washed with brine, dried over sodium sulfate, filtered and concentrated. The yellow oil is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 5/1). 1.6 g of of the desired compound are obtained in the form of a yellow oil (70% of the theoretical yield).
[0205] 1H-NMR (DMSO-D6): 8.80 ppm (d, 1H); 8.48 ppm (d, 1H); 4.11 ppm (s, 3H).
[0206] The 5-pyridylpyrazole isomer is obtained in an analogous manner in a 90% yield (crude).
[0207] 1H-NMR (CDCl3): 8.66 ppm (d, 1H); 7.95 ppm (d, 1H); 3.83 ppm (s, 3H).
Example P13: 3-(3-Fluoro-5-chloro-2-pyridyl)-5-hydroxy-1-methyl-[1H]-pyrazole[0208] 57
[0209] 110.6 g of malonic acid monomethyl ester · potassium salt are introduced into 500 ml of absolute acetonitrile. With stirring, the mixture is cooled in an ice-bath and 109 ml of triethylamine are added dropwise. 84.3 g of anhydrous magnesium chloride are then added. A slight exothermic reaction is observed. After removal of the icebath, the mixture is stirred for 2 hours at 25° C. After cooling again in an ice-bath, 68.7 g of 3-fluoro-5-chloro-2-pyridine-carboxylic acid chloride (Example P6) are added in several portions and 300 ml of absolute acetonitrile are added. A thick slurry gradually forms. The cooling bath is removed and the slurry is then stirred for 5 hours. The reaction mixture is subsequently poured into 3 liters of ice-water and 200 ml of concentrated hydrochloric acid, and then stirred for 15 minutes and extracted with ethyl acetate. The organic phase is washed with water and brine, dried over sodium sulfate, filtered and concentrated to dryness in vacuo. 110 g of a brown oil are obtained, which is used directly for the next reaction step.
[0210] For that reaction step, the brown oil obtained above is introduced at 25° C. into a solution of 20.5 ml of methyl hydrazine in 300 ml of glacial acetic acid and then stirred for 2 hours at 85° C. After the resulting brown suspension has been cooled to 25° C. it is introduced in portions into 2.5 liters of ice-water, stirred for 1 hour, filtered and washed with water and n-hexane. After drying at 60° C. in vacuo, 65.8 g of the desired title compound having a melting point of 195-199° C. are obtained.
Example P14: 3-(3-Fluoro-5-chloro-2-pyridyl)-5-difluoromethoxy-1-methyl-[1H]-pyrazole[0211] 58
[0212] 46.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-hydroxy-1-methyl-[1H]-pyrazole (Example P13) and 84 g of potassium carbonate are introduced into 250 ml of dry dimethylformamide and heated to 85° C. While stirring well, Freon 22 (chlorodifluoromethane) is then introduced for a period of 2 hours. TLC analysis of a worked-up sample (silica gel 60 F254; eluant: n-hexane/ethyl acetate/glacial acetic acid 20/20/1, UV) shows that there is no starting material present. The reaction mixture is partitioned between water and diethyl ether (foaming occurs on the addition of water). After extraction by shaking, and separation of the phases, the ethereal phase is washed twice with water and once with brine. After drying the organic phase over sodium sulfate and filtration, concentration in vacuo is carried out and the residue is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v)). 22.0 g of the desired title compound are obtained in the form of a light-yellow solid.
[0213] 1H-NMR (CDCl3): 8.51 ppm (broad signal, 1H); 7.56 ppm (dxd, 1H); 6.61 ppm (t, 1H); 6.53 ppm (d, 1H); 3.89 ppm (s, 3H).
Example P15: 3-(3-Fluoro-5-chloro-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole[0214] 59
[0215] 17.92 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P14) are introduced into 60 ml of glacial acetic acid together with 10.6 g of sodium acetate. With stirring, the mixture is heated to 60° C. and a saturated solution of chlorine in glacial acetic acid is added until TLC analysis of a worked-up sample shows that the reaction is complete (silica gel 60 F254; eluant: n-hexane/ethyl acetate 2/1; UV; Rf value of the starting material 0.34; Rf value of the product 0.48). The mixture is then concentrated to dryness in vacuo and the residue obtained is partitioned between sodium hydrogen carbonate solution and ethyl acetate. The organic phase is washed with brine, dried over sodium sulfate, filtered and concentrated to dryness by evaporation in vacuo. 19.8 g of the desired target compound (pure according to TLC) having a melting point of 95-96° C. are obtained.
Example P16: 3-(3-Fluoro-5-chloro-2-pyridyl)-4-formyl-5-difluoromethoxy-1-methyl-[1H]-pyrazole[0216] 60
[0217] With cooling in an ice-bath, 2.41 ml of phosphorus oxychloride are introduced into 5 ml of N,N-dimethylformamide and the mixture is then stirred for 2 hours at 25° C. The mixture is then added dropwise at 80° C. to 5.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-hydroxy-1-methyl-[1H]-pyrazole (Example P13) in 15 ml of N,N-dimethylformamide over a period of 30 minutes. After subsequently stirring for 1.5 hours at 80° C., the mixture is cooled to 25° C. and ice and then water are added and extraction is carried out with diethyl ether. The organic phase is washed with water and dried over sodium sulfate to yield 1.1 g of a yellow solid as intermediate. The solid is introduced together with 1.72 g of pulverised anhydrous potassium carbonate into 10 ml of dry N,N-dimethylformamide. While stirring well, the mixture is heated to 75° C. and freon 22 (CHCIF2) is slowly introduced for a period of 7 hours. The mixture is then cooled to 25° C. and taken up in diethyl ether. The ethereal phase is washed with water and then with brine, dried over sodium sulfate, filtered and concentrated. 1.50 g of crude product are obtained in the form of a brown solid, which is purified using a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 4/1 (v/v)). In that manner 0.14 g of the desired target compound is obtained in the form of a yellow solid having a melting point of 111-116° C.
Example P17: 3-(3-Fluoro-5-chloro-2-pyridyl)-4-difluoromethyl-5-difluoromethoxy-1-methyl-[1H]-pyrazole[0218] 61
[0219] 0.13 g of 3-(3-fluoro-5-chloro-2-pyridyl)-4-formyl-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P16) is introduced into 3.0 ml of dry 1,2-dichlorethane. With stirring, 0.11 ml of diethylamino-sulfur trifluoride (DAST is added dropwise using a syringe, the reaction mixture taking on a dark colour. The mixture is then stirred for 1 hour at 50° C. The reaction solution is cooled to 25° C. and applied directly to a flash chromatography column (silica gel) and eluted with n-hexane/ethyl acetate 5/1 (v/v). 0.07 g of the desired compound is obtained in the form of a light-yellow oil having a melting point of 79-81° C.
Example P18: 3-(3-Fluoro-5-chloro-2-pyridyl)-5-bromo-1-methyl-[1H]-pyrazole[0220] 62
[0221] 20.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-hydroxy-1-methyl-[1H]-pyrazole (Example P13) are introduced into 80 ml of tetrachloroethane. A total of 25.2 g of phosphorus oxybromide (POBr3) is added in portions to the brown suspension. The mixture is then stirred for 2 hours at an internal temperature of 130° C., after which it is cooled and, with cooling with an ice-bath, 150 ml of a 2M sodium hydroxide solution are added dropwise. After the addition of diethyl ether and separation of the phases, the organic phase is washed in succession with water, dilute hydrochloric acid and brine, dried over sodium sulfate, filtered and concentrated to dryness in vacuc. 19.94 g of a brown solid (crude product) are obtained, which is purified by means of digestion with 50 ml of n-hexane. 12.65 g of the desired compound are obtained in the form of a brown solid having a melting point of 110-111° C.
Example P19: 5-(5-Chloro-3-fluoro-2-pyridyl)-2-methyl-[2H]-pyrazole-3-carboxylic acid ethyl ester[0222] 63
[0223] 5.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-bromo-1-methyl-[1H]-pyrazole (Example P18) are introduced into an autoclave together with 7.2 ml of triethylamine, 0.48 g of bis-triphenyl-phosphinepalladium dichloride (PdCl2(PPh3)2) and 70 ml of absolute ethanol. At 22° C. a pressure of 100 bar is applied with carbon monoxide and the reaction mixture is maintained at 100° C. for 48 hours. In the meantime a further 0.48 g of bis-triphenylphosphinepalladium dichloride is added, and the mixture is then cooled to 22° C. and the pressure is released. The reaction mixture is filtered over Hyflo and, after evaporating off the ethanol, taken up in ethyl acetate. The ethyl acetate phase is washed with dilute hydrochloric acid and then with brine, dried over sodium sulfate, filtered and finally concentrated to dryness in vacuc. 3.17 g of a brown solid are obtained, which is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v)). 2.31 g of the desired title compound are obtained in the form of a light-yellow solid having a melting point of 117-118° C.
Example P20: 5-(5-Chloro-3-fluoro-2-pyridyl)-4-chloro-2-methyl-[2H]-pyrazole-3-carboxylic acid ethyl ester[0224] 64
[0225] 22.9 g of 5-(5-chloro-3-fluoro-2-pyridyl)-2-methyl-[2H]-pyrazole-3-carboxylic acid ethyl ester (Example P19) are introduced together with 19.9 g of sodium acetate into 300 ml of glacial acetic acid at a temperature of 65° C. With stirring, 6.3 g of chlorine gas are passed over the solution at that temperature in the course of 1 hour. The reaction mixture is then poured into 2.5 liters of ice-water and subsequently stirred for 20 minutes. The resulting precipitate is filtered off, washed with ice-water and then dried in vacuo at 50° C. 24.4 g of the desired title compound are obtained in the form of a yellow solid having a melting point of 77-79° C.
Example P21: 5-(5-Chloro-3-fluoro-2-pyridyl)-4-chloro-2-methyl-[2H]-pyrazole-3-carboxylic acid[0226] 65
[0227] 11.0 g of 5(5-chloro-3-fluoro-2-pyridyl)-4-chloro-2-methyl-[2H]-pyrazole-3-carboxylic acid ethyl ester (Example P20) are introduced into 60 ml of dimethyl sulfoxide at 22° C. With stirring, 25.9 ml of a 2N aqueous sodium hydroxide solution are added dropwise, in the course of which an exothermic reaction can be detected. After subsequently stirring for one hour, TLC analysis of a sample shows that all the starting material has reacted. The reaction mixture is introduced into 2 liters of ice-cold dilute hydrochloric acid, then stirred for 15 minutes and filtered over a paper filter. The filtration residue is washed with cold water and, after drying overnight at 60° C. in vacuo, 8.7 g of the desired title compound having a melting point of 230° C. (decomposition) are obtained.
[0228] The Rf value of the starting material on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 1/1 (v/v)) is 0.75; and the Rf value of the desired title compound is 0.36.
Example P22: 3-(3-Fluoro-5-chloro-2-pyridyl)-4-chloro-5-trifluoromethyl-1-methyl-[H]-pyrazole[0229] 66
[0230] 8.63 g of 5-(5-chloro-3-fluoro-2-pyridyl)-4-chloro-2-methyl-[2H]-pyrazole-3-carboxylic acid (Example P21) are introduced into a fluorination unit with 27 g of hydrogen fluoride (HF), 16.2 g of sulfur tetrafluoride (SF4) and 270 ml of methylene chloride. The mixture is maintained at 80° C. for 5 hours. It is then cooled to 22° C. and the SF4 is removed by way of a gas destroying unit (argon stream) and the HF is removed using a water-jet vacuum. After the addition of methylene chloride, the reaction mixture is extracted three times with ice-water, and the organic phase is dried over sodium sulfate and then concentrated to dryness in vacuo together with 40 g of silica gel. After applying the silica gel to a flash chromatography column, elution is carried out with an n-hexane/ethyl acetate 5/1 (v/v) mixture. 5.48 g of the desired title compound are obtained in the form of a beige solid having a melting point of 76-78° C.
Example P23: 3-(5,6-Dichloro-2-pyridyl)- and 3-(4,5-dichloro-2-pyridyl)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole (isomers A and B)[0231] 67
[0232] 20 ml of phosphorus oxychloride are heated to 90° C. With stirring, 10.37 g of 3-(5-chloro-2-pyridyl-N-oxide)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole (Example P25) are introduced in several portions at that temperature and the mixture is then stirred for 1 hour at 90° C. The phosphorus oxychloride is then evaporated off in vacuo, the residue is taken up in diethyl ether and the ethereal phase is subsequently washed in succession with water, 0.5M sodium hydroxide solution and brine. After drying over sodium sulfate and filtering, concentration in vacuo is carried out and the residue obtained (8.93 g) is purified by column chromatography (silica gel; eluant: n-hexane/ethyl acetate 10/1). First 0.57 g of isomer B and then 5.11 g of isomer A are isolated in the form of a white solid.
[0233] On silica gel 60 F254 using the eluant n-hexane/ethyl acetate 4/1 (v/v), the Rf value of isomer A is 0.31 and the Rf value of isomer B is 0.41.
[0234] The treatment of 6.3 g of 3-(5-chloro-2-pyridyl-N-oxide)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole (Example P25) for 1 hour at 90° C. with 6.3 g of phosphorus pentachloride in 20 ml of phosphorus oxychloride yields, after working up as above, 4.36 g of isomer A and 1.01 g of isomer B.
Example P24: 3-(3-Fluoro-5.6-dichloro-2-pyridyl-N-oxide)4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole[0235] 68
[0236] 1.5 g of 3-(3-fluoro-5,6-dichloro-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole are dissolved in 10 ml of 1,2-dichloroethane and 0.5 g of hydrogen peroxide/urea adduct is added. With cooling in an ice-bath, 0.66 ml of trifluoroacetic anhydride is then metered in using a syringe and the mixture is stirred at 22° C. for 3 hours. According to TLC analysis there is only partial reaction of the starting material. Consequently, 0.5 g of hydrogen peroxide/urea adduct and 0.66 ml of trifluoroacetic anhydride are added to the reaction mixture one after the other, in the manner described above, four times, followed each time by stirring for 3 hours at 22° C., in the course of which a yellow suspension is formed which is taken up in ethyl acetate. The organic phase is washed in succession with 1N sodium hydroxide solution, water and brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product is purified by means of flash chromatography (silica gel; eluant: hexane/ethyl acetate 3/2). 0.25 g of the desired product is obtained in the form of yellow crystals having a melting point of 114-118° C.
Example P25: 3-(5-Chloro-2-pyridyl-N-oxide)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole[0237] 69
[0238] 6.82 g of 3-(5-chloro-2-pyridyl)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole are introduced into 30 ml of methylene chloride at 250° C. With stirring, 7.23 g of m-chloroperbenzoic acid are added. After 48 hours a further 2.50 g of m-chloroperbenzoic acid are added. After a further 24 hours the reaction mixture is taken up in ethyl acetate and extracted twice with dilute sodium hydroxide solution, then washed with brine, dried over sodium sulfate and concentrated. Chromatography is then carried out (silica gel; eluant: n-hexane/ethyl acetate 1/1 (v/v)). 6.31 g of the desired compound are isolated in the form of a white solid.
[0239] 1H-NMR (DMSO-D6): 8.75 ppm (d, 1H); 7.66 ppm (d, 1H); 7.59 ppm (dxd, 1H); 4.08 ppm (s, 3H).
[0240] Starting from the 5-(5-chloro-2-pyridyl)-4-chloro-3-trifluoromethyl-1-methyl-[1H]-pyrazole isomer, the 5-(5-chloro-2-pyridyl-N-oxide)-4-chloro-3-trifluoromethyl-1-methyl-[1H]-pyrazole isomer can be obtained in a yield of 70%. 70
Example P26: 3-(3-Fluoro-5-chloro-2-pyridyl-N-oxide)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole[0241] 71
[0242] 0.57 g of 3-(3-fluoro-5-chloro-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P15) is introduced into 5 ml of methylene chloride and 0.63 g of a 55% m-chloroperbenzoic acid is added. After stirring for 4 days at 25° C., the crude mixture is taken up in ethyl acetate and washed in succession with sodium hydrogen carbonate solution, water and brine. After drying over sodium sulfate and filtering, concentration is carried out and the residue is purified by means of flash chromatography. 0.45 g of the desired target compound is obtained in the form of a white solid having a melting point of 115-120° C.
Example P27: 3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol[0243] 72
[0244] 1.0 g of 3-(3-fluoro-5-chloro-2-pyridyl-N-oxide)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P26) is introduced into 12 ml of dry N,N-dimethylformamide. With stirring and cooling with an ice-bath, 4.2 ml of trifluoroacetic anhydride are added dropwise from a syringe and the mixture is subsequently stirred overnight at 25° C. The mixture is then concentrated by evaporation in vacuo and the residue is partitioned between diethyl ether and water. After extraction by shaking, and separation of the phases, the ethereal phase is washed with dilute aqueous sodium hydrogen carbonate soolution and brine, dried over sodium sulfate, filtered and concentrated. 1.23 g of a yellow oil are obtained, which is purified using a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 2/3 (v/v) and 1% glacial acetic acid). 0.59 g of the desired compound is obtained in the form of a yellow solid having a melting point of 126-128° C.
Example P28: 5-(5-Chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carboxylic acid[0245] 73
[0246] 6.75 g of 5-(5-chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carboxylic acid ethyl ester are suspended in 40 ml of dimethyl sulfoxide. With occasional cooling in an ice-bath (internal temperature <30° C.), 14.3 ml of a 2N sodium hydroxide solution are added dropwise. The thick, yellowish-brown suspension is stirred at 22° C. for 2 hours. The suspension is then introduced into ice-water and adjusted to pH 1 with 2N hydrochloric acid. The resulting slurry is filtered, washed well with cold water and then dried in vacuo at 60° C. 5.97 g of the desired title compound are obtained in the form of a beige solid having a melting point of 194-196° C.
Example P29: 5-(5-Chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carboxylic acid amide[0247] 74
[0248] 3.0 g of 5-(5chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carboxylic acid (Example P28) are introduced into 25 ml of 1,2-dichloroethane and, at 80° C., a total of 1.21 ml of thionyl chloride is added and the mixture is subsequently stirred for 5 hours at 80° C. The mixture is concentrated in vacuo, 20 ml of carbon tetrachloride are added three times and each time the mixture is concentrated to dryness by evaporation.
[0249] The resulting acid chloride is introduced into 35 ml of tetrahydrofuran. With cooling in an ice-bath, ammonia gas is introduced. A brown precipitate forms. Stirring is carried out overnight at 22° C. The resulting suspension is introduced into five times its volume of ice-water. After then stirring briefly, filtration is carried out and the filtration residue is subsequently washed with cold water and dried in vacuo at 60° C. 2.0 g of the desired title compound are obtained in the form of a brown solid having a melting point of 201-204° C.
Example P30: 5-(5-Chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carbonitrile[0250] 75
[0251] 1.82 g of 5-(5-chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carboxylic acid amide (Example P29) are suspended in 20 ml of dioxane. With cooling with an ice-bath, first 1.65 ml of pyridine and then 1.44 ml of trifluoroacetic anhydride are added. After 5 minutes the cooling bath is removed and the mixture is subsequently stirred for 1 hour at 22° C. The brownish-red solution is diluted with diethyl ether and washed with 1N hydrochloric acid and then with brine. The mixture is dried over sodium sulfate and filtered and then directly concentrated with twice the amount of silica gel. After application of the silica gel to a flash chromatography column, elution is carried out with n-hexane/ethyl acetate 4/1 (v/v). 1.60 g of the desired title compound are obtained in the form of a beige solid having a melting point of 144-146° C.
Example P31: 3-(3-Fluoro-5-methyl-2-pyridyl)-4-chloro-5difluoromethoxy-1-methyl-[1H]-pyrazole[0252] 76
[0253] 2.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P15) are introduced into 6 ml of absolute dioxane. In order to remove the oxygen, gentle evacuation is carried out three times (waterjet pump) and the mixture is gassed with argon. 6.4 ml of a 2M solution of trimethylaluminium in toluene and 0.10 g of tetrakis-triphenylphosphinepalladium (Pd(PPh3)4) are added thereto. The mixture is heated to 90° C., with stirring, in an argon atmosphere. The next day the mixture is cooled to 22° C., a further 0.10 g of Pd(PPh3)4 and 6.4 ml of a 2M solution of trimethylaluminium in toluene are added and the mixture is stirred at 110° C. After 4 hours, TLC analysis of a worked-up sample shows that all the starting material has reacted. The reaction mixture is introduced carefully into cold, dilute hydrochloric acid and is then extracted with ethyl acetate. The combined organic phases are washed with brine, dried over sodium sulfate, filtered and concentrated by evaporation in vacuo. The crude product obtained is purified over a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 1/1 (v/v)). 1.36 g of the desired compound are obtained in the form of a yellow oil, which slowly crystallises; melting point 41-42° C.
[0254] The Rf value of the starting material on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 2/1 (v/v)) is 0.37 and the Rf value of the title compound is 0.15.
Example P32: 3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-hydroxy-[1H]-pyridin-2-one[0255] 77
[0256] 0.50 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol (Example P27) is introduced into 4 ml of 1,2-dichloroethane, and 0.15 g of hydrogen peroxide/urea adduct (30%) and 0.22 ml of trifluoroacetic anhydride are added. The mixture is stirred overnight at 22° C. and then a further 0.15 g of hydrogen peroxide/urea adduct is added together with 0.22 ml of trifluoroacetic anhydride. The mixture is subsequently stirred for 5 hours and then partitioned between ethyl acetate and dilute hydrochloric acid. The separated organic phase is washed with brine, dried over sodium sulfate, filtered and concentrated to dryness. 0.55 g of the desired compound is obtained in the form of a yellow resinous precipitate (crude product).
[0257] 1H-NMR (CDCl3): 7.65 ppm (d, 1H); 6.74 ppm (t, 1H); 3.90 ppm (s, 3H).
Example P33: 3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-methoxy-[1H]-pyridin-2-one[0258] 78
[0259] 0.20 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-hydroxy-[1H]-pyridin-2-one (Example P32) is introduced into 2 ml of N-methylpyrrolidone (NMP) at 22° C. and 0.16 g of anhydrous potassium carbonate is added. With stirring, 0.10 g of methyl iodide in 0.5 ml of NMP is then added dropwise. The reaction mixture is stirred for 2 hours at 22° C. and then partitioned between 20 ml of water and diethyl ether. The separated ethereal phase is washed with brine, dried over sodium sulfate, filtered and concentrated to dryness by evaporation in vacuo. 0.13 g of the desired crude product is obtained in the form of a yellow oil which, after purification by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 1/1 (v/v)), yields 0.08 g of pure product in the form of a colourless oil.
[0260] 1H-NMR (CDCl3): 7.62 ppm (d, 1H); 6.74 ppm (t, 1H); 4.00 ppm (s, 3H); 3.90 ppm (s, 3H).
Example P34: 3-(5-Chloro-3-fluoropyridin-2-yl)-2-methyl-3-oxopropionic acid tert-butyl ester[0261] 79
[0262] 32.3 g of diisopropylamine are introduced into 200 ml of tetrahydrofuran and, with cooling with a Co2/acetone cooling bath, 200 ml of a 1.6M solution of n-butyllithium in hexane are added dropwise. 49.2 ml of propionic acid tert-butyl ester are then added dropwise at approximately −75° C. and the mixture is stirred at that temperature for 45 minutes. At approximately −75° C. a solution of 32.6 g of 3-fluoro-5-chloro-2-pyridinecarboxylic acid ethyl ester (Example P1) in 40 ml of tetrahydrofuran (THF) is then added dropwise and the mixture is stirred at that temperature for 1 hour, after which it is diluted with 250 ml of tert-butyl methyl ether. A mixture of 100 ml of water and 200 ml of glacial acetic acid is added, the phases are separated, the aqueous phase is extracted again, and the combined organic phases are washed with water. After drying over magnesium sulfate, filtration and concentration to dryness in vacuo are carried out. 51 g of the desired compound are obtained in the form of an oil (crude product).
[0263] The Rf value of the starting material on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 3/1 (v/v)) is 0.46, and the Rf value of the product is 0.63.
Example P35: 3-(5-Chloro-3-fluoropyridin-2-yl)-2-methyl-3-oxopropionic acid[0264] 80
[0265] 25.5 g of 3-(5-chloro-3-fluoropyridin-2-yl)-2-methyl-3-oxopropionic acid tert-butyl ester (Example P34) are added dropwise to 30 ml of a 33% solution of hydrogen bromide (HBr) in glacial acetic acid to form a suspension. The mixture is subsequently stirred for 90 minutes and then introduced into 300 ml of ice-water. The resulting precipitate is filtered off, washed with water and dried. 15.9 g of the desired title compound are obtained in the form of a solid having a melting point of 101-102° C.
Example P36: 2-Chloro-1-(5-chloro-3-fluoropyridin-2-yl)-propan-1-one[0266] 81
[0267] 20.8 g of 3-(5-chloro-3-fluoropyridin-2-yl)-2-methyl-3-oxopropionic acid (Example P35) are introduced into 125 ml of glacial acetic acid. 6.3 g of chlorine gas are introduced into the solution in the course of 1 hour. The mixture is then poured into 700 ml of water and extracted with tert-butyl methyl ether. The combined ethereal phases are washed with water and dried over magnesium sulfate, filtered and concentrated by evaporation in vacuo. The crude product is dissolved in 180 ml of tert-butyl methyl ether, 45 g of silica gel are added and the mixture is stirred for 30 minutes, in the course of which the evolution of gas observed initially comes to a halt. The silica gel is then filtered off and subsequently washed and the combined ethereal phases are concentrated to dryness in vacuo. 20.1 g of an oily crude product are obtained, which is purified over a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 4/1 (v/v)). 17.0 g of the desired title compound are obtained in the form of a solid having a melting point of 29-32° C.
Example P37: 5-(5-Chloro-3-fluoropyridin-2-yl)-3,6-dimethyl-3,6-dihydro-[1,3,4]-thiadiazine-2-thione[0268] 82
[0269] 19.1 ml of a 4N sodium hydroxide solution and 3.5 g of methyl hydrazine are introduced into 76 ml of ethanol. At an internal temperature of <5° C., 4.5 ml of carbon disulfide are added dropwise with stirring, and the mixture is then stirred for 30 minutes. 17.0 g of 2-chloro-1-(5-chloro-3-fluoropyridin-2-yl)-propan-1-one (Example P36) are subsequently added in the course of 15 minutes at an internal temperature of <5° C. The temperature is then allowed to rise to 22° C. and the mixture is subsequently stirred for 30 minutes. TLC analysis (silica gel 60 F254; eluant: n-hexane/ethyl acetate, UV) of a worked-up sample shows that starting material is no longer present. 2.5 ml of a concentrated hydrochloric acid solution are then added dropwise to form a yellow precipitate. Stirring is carried out for 1 hour and the mixture is then poured into water and extracted with tert-butyl methyl ether. The combined ethereal phases are washed with water, dried over magnesium sulfate, filtered and concentrated to dryness in vacuo. 20.3 g of the desired title compound are obtained in the form of a solid having a melting point of 107-112° C.
Example P38: 5-Chloro-2-(1,4-dimethyl-5-methylsulfanyl-[1H]-pyrazol-3-yl)-3-fluoropyridine[0270] 83
[0271] 21.6 g of crude 5-(5-chloro-3-fluoropyridin-2-yl)-3,6-dimethyl-3,6dihydro-[1.3.4]-thiadiazine-2-thione (Example P37) are introduced into 70 ml of tert-butanol, 19.1 g of triphenylphosphine are added and the mixture is stirred at an internal temperature of 65° C. for approximately 15 minutes, a clear solution forming. After cooling to 22° C., a suspension again forms, to which 8.2 g of potassium tert-butanolate are added in portions at an internal temperature of <40° C. (cooling with an ice-bath). The mixture is then stirred overnight, subsequently poured into 600 ml of water, stirred, filtered and washed, and the aqueous phase is extracted thoroughly with tert-butyl methyl ether. The aqueous phase is rendered strongly acidic with concentrated hydrochloric acid and extracted with tert-butyl methyl ether. The combined ethereal phases are washed with water, dried over magnesium sulfate, filtered and concentrated to dryness in vacuo. 6.8 g of a crude intermediate are obtained.
[0272] 1.9 g of the intermediate are dissolved in 10 ml of dimethylformamide (DMF) and 2.2 g of potassium carbonate are added. 0.5 ml of methyl iodide in 2 ml of DMF is then added dropwise. The mixture is subsequently stirred at 22° C. for 5 hours, poured into 120 ml of ice-water, and extracted with diethyl ether. The combined ethereal phases are washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. 1.8 g of an oil are obtained, which is purified over a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v)). 1.3 g of the desired title compound are obtained in the form of a solid having a melting point of 61-64° C.
Example P39: 5-Chloro-2-(1,4-dimethyl-5-methylsulfanyl-[1H]-pyrazol-3-yl)-3-fluoropyridine[0273] 84
[0274] 2.1 g of 5-chloro-2-(1,4-dimethyl-5-methylsulfanyl-[1H]-pyrazol-3-yl)-3-fluoropyridine (Example P38) are dissolved in 40 ml of methylene chloride, and 2.84 g of 70% meta-chloroperbenzoic acid are added in portions. The mixture is then stirred for 4 hours at 22° C. and subsequently stirred with 1N sodium hydrogen carbonate solution for 30 minutes. The organic phase is separated off, washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. 1.7 g of a solid are obtained, which is purified over a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 1/1 (v/v)). 0.80 g of the desired sulfone having a melting point of 145-147° C. and 0.70 g of the sulfoxide having a melting point of 112-114° C. are obtained.
Example P40: 5-Chloro-3-fluoro-2-(5methanesulfonyl-1,4-dimethyl-[1H]-pyrazol-3-yl)-pyridine-1-oxide[0275] 85
[0276] 5.3 g of 5-chloro-2-(1,4-dimethyl-5-methylsulfanyl-[1H]-pyrazol-3-yl)-3-fluoropyridine (Example P39) are dissolved in 50 ml of methylene chloride. With stirring, 19.2 g of 70% m-chloroperbenzoic acid (MCPBA) are introduced in portions at 22° C. with exothermic reaction. The mixture is then stirred overnight at 22° C. The next day, a further 4.9 g of MCPBA are added and the mixture is stirred overnight. The mixture is subsequently extracted with dilute sodium hydrogen carbonate solution and then with sodium thiosulfate solution. The extract is dried over magnesium sulfate and then filtered and concentrated to dryness in vacuo. The crude product (6 g) is purified over silica gel using ethyl acetate as eluant. 3.6 g of the desired title compound having a melting point of 174-176° C. are obtained.
Example P41: 3-Chloro-5-fluoro-6-(5-methanesulfonyl-1,4-dimethyl-[1H]-pyrazol-3-yl)-[1H]-pyridin-2-one[0277] 86
[0278] 2.6 g of 5-chloro-3-fluoro-2-(5-methanesulfonyl-1,4-dimethyl-[1H]-pyrazol-3-yl)-pyridine-1-oxide (Example P40) are introduced into 35 ml of dry dimethylformamide. At a temperature of 10° C., 16.8 g of trifluoroacetic anhydride are added dropwise and the mixture is then stirred overnight at 22° C., subsequently poured into 2 liters of ice-water and extracted with tert-butyl methyl ether. After drying over magnesium sulfate, filtering and concentrating to dryness by evaporation in vacuo, 1.8 g of the desired compound are obtained as crude product, which can be used directly in the next step.
Example P42: 3-Chloro-5-fluoro-6-(5-methanesulfonyl-1,4-dimethyl-[1H]-pyrazol-3-yl)-1-propyn-2-yl-[1H]-pyridin-2-one[0279] 87
[0280] 1.8 g of 3-chloro-5-fluoro-6-(5-methanesulfonyl-1,4-dimethyl-[1H]-pyrazol-3-yl)-[1H]-pyridin-2-one (Example P41) are dissolved in 10 ml of dimethyl sulfoxide and 3.0 ml of a 2N aqueous sodium hydroxide solution are added (slightly exothermic reaction). After subsequently stirring for 30 minutes at 22° C., 0.46 ml of propargyl bromide is added dropwise and the mixture is further stirred overnight at 22° C. The reaction mixture is then introduced into 120 ml of ice-water, filtered, and washed with water. It is taken up in ethyl acetate, dried over magnesium sulfate, filtered and concentrated to dryness by evaporation in vacuo. The crude product is purified by means of silica gel chromatography (eluant: n-hexane/ethyl acetate 1/1 (v/v)). 0.74 g of the desired title compound, which still contains 20% of the isomeric O-propargyl derivative, is obtained; m.p. 189-192° C.
[0281] The Rf value of the title compound on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 1/1 (v/v)) is 0.28, the Rf value of the O-propargyl isomer is 0.55, and the Rf value of the starting compound is 0.05.
Example P43: 5-(5-Chloro-3-fluoro-1-methyl-6-oxo-1,6-dihydropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carbonitrile[0282] 88
[0283] 1.54 g of 3-chloro(1,4-dimethyl-5-cyano-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol are introduced into a mixture of 20 ml of absolute 1,2-dimethoxyethane and 5 ml of absolute dimethylformamide at 22° C. With stirring, first 1.20 g of lithium bromide are added and then, 10 minutes later, in portions, 0.28 g of a 60% sodium hydride dispersion in oil. After a further 10 minutes, 0.86 ml of methyl iodide is added, after which the mixture is stirred overnight at 90° C. The mixture is then cooled to 22° C., carefully poured into dilute hydrochloric acid, and extracted with diethyl ether. The combined ethereal phases are washed with brine, dried over sodium sulfate, filtered and concentrated in vacuc together with 4 g of silica gel. The silica gel is applied to a flash chromatography column and fractionated by means of gradient elution using n-hexane/ethyl acetate 3/1 to 1/1 (v/v). 0.68 g of the desired compound is obtained in the form of a white solid having a melting point of 190-191 ° C.
Example P44: 1-Allyl-3-chloro-6-(4-chloro-5-difuoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-[1H]-pyridin-2-one[0284] 89
[0285] 1.50 g of 3-(3-fluoro-5-chloro-6-hydroxy-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P27) are suspended in a dry mixture of 16 ml of dimethoxyethane and 4 ml of N,N-dimethylformamide (DMF). With stirring, a total of 0.20 g of a 55% sodium hydride dispersion is added, in portions, at 250° C. The suspension is subsequently stirred for ten minutes, 0.79 g of anhydrous lithium bromide is then added and, after a further fifteen minutes' stirring, 0.77 ml of allyl bromide is added dropwise. The mixture is subsequently stirred overnight at 65° C. The next day, TLC analysis of a worked-up sample shows that starting material is no longer present. The reaction mixture is cooled to 25° C. and partitioned between dilute hydrochloric acid and tert-butyl methyl ether. After extraction by shaking, and separation of the phases, the ethereal phase is washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo together with 5 g of silica gel. The silica gel is applied to a flash chromatography column and chromatography is carried out (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v)). 0.95 g of the target compound is obtained in the form of a slightly yellowish-brown-coloured oil, the Rf value of which on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 1/1 (v/v)) is 0.33.
Example P45: 1-Ethyl-3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-[1H]-pyridin-2-one[0286] 90
[0287] 1.5 g of 3-(3-fluoro-5-chloro-6-hydroxy-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P27) are introduced into 6 ml of dimethyl sulfoxide (DMSO). 2.5 ml of a 2N aqueous sodium hydroxide solution are added thereto. 0.78 g of ethyl iodide in 2 ml of DMSO is then added dropwise, with stirring, and the mixture is further stirred overnight at 70° C. The next day, the reaction mixture is partitioned between dilute hydrochloric acid and diethyl ether. After extraction by shaking, and separation of the phases, the ethereal phase is washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. Finally, the residue is purified over a flash chromatography column (silica gel; elution gradient: n-hexane/ethyl acetate 4/1 to 1/1 (v/v)). 0.54 g of the desired target compound is obtained in the form of a yellow oil having an Rf value of 0.17 on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 2/1 (v/v)).
Example P46: 3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid benzyl ester[0288] 91
[0289] 10.0 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol (Example P27) are introduced into a mixture of 100 ml of dimethoxyethane and 25 ml of dimethylformamide at 22° C. 1.22 g of sodium hydride (60%, moistened in oil) are then added in portions, evolution of gas being observed. After subsequently stirring for 15 minutes at 22° C., 5.3 g of dry lithium bromide are added (slightly exothermic reaction) and, after 10 minutes, 9.6 ml of bromoacetic acid benzyl ester are added. The mixture is then stirred for 5 hours at 75° C. After cooling to 22° C., the mixture is taken up in ethyl acetate, washed with dilute hydrochloric acid and then with brine, subsequently dried over sodium sulfate, filtered, and concentrated to dryness in vacuo. 24.3 g of a yellow oil are obtained, which is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v)). 7.67 g of the desired compound are obtained in the form of a yellow oil which crystallises on being left to stand; m.p. 83-85° C.
[0290] The Rf value of the starting material on silica gel 60 F254 (eluant: n-hexane/ethyl acetate/glacial acetic acid 20/20/1 (v/v/v)) is 0.45, and the Rf value of the title compound is 0.60. The isomeric O-alkyl derivative is isolated as secondary product.
Example P47: 3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid[0291] 92
[0292] 6.0 g of 3-(3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid benzyl ester (Example P46) are hydrogenated at normal pressure and 22° C. with 0.35 g of 5% palladium-on-active carbon in 90 ml of tetrahydrofuran (THF). After 2.5 hours, the reaction mixture is filtered over Hyflo and washed with THF. 5.11 g of the desired title compound are obtained in the form of a colourless resin, which solidifies on being left to stand.
[0293] 1H-NMR (CDCl3): 7.58 ppm (d, 1H); 6.66 ppm (t, 1H); 4.73 ppm (s, 2H); 3.77 ppm (s, 3H).
Example P48: 3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid imidazolide[0294] 93
[0295] 2.0 g of 3-(3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid (Example P47) are suspended in 20 ml of 1,2-dichloroethane. With stirring, 0.92 g of 1,1′-carbonyldiimidazole is added at 22° C. The mixture is stirred overnight and the resulting solution is concentrated to dryness by evaporation in vacuo. 2.40 g of the desired title compound are obtained in the form of a beige solid, which contains 20% by weight imidazole.
[0296] 1H-NMR (DMSO-D6): 8.51 ppm (s, 1H); 8.41 ppm (d, 1H); 7.77 ppm (m, 1H); 7.33 ppm (t, 1H); 7.13 ppm (m, 1H); 5.46 ppm (s, 2H); 3.60 ppm (s, 3H).
Example P49: 3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid diethylamide[0297] 94
[0298] 1.0 g of 3-(3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid (Example P47) is introduced into 8 ml of 1,2-dichloroethane. 0.50 g of carbonyldiimidazole is added to the white suspension and the mixture is stirred for one hour at 22° C., in the course of which all undissolved components dissolve. 0.39 ml of diethylamine is then added and the mixture is stirred overnight at 22° C. The next day, the reaction mixture is taken up in ethyl acetate and washed in succession with dilute sodium hydrogen carbonate solution, dilute hydrochloric acid and brine. After drying over sodium sulfate, filtration is carried out and the residue is concentrated to dryness in vacuo. 1.20 g of a yellow oil is obtained which is purified over a flash chromatography column (silica gel; eluant: ethyl acetate). 1.27 g of the desired title compound are obtained in the form of a colourless resin.
[0299] 1H-NMR (CDCl3): 7.61 ppm (d, 1H); 6.72 ppm (t, 1H); 4.99 ppm (s, 2H); 3.82 ppm (s, 3H); 3.27 ppm (m, 4H); 1.13 ppm (t, 3H); 1.04 ppm (t, 3H).
Example P50: 3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid allylamide[0300] 95
[0301] 1.0 g of 3-(3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl) -5-fluoro-2-oxo-[2H]-pyridin1-yl)-acetic acid imidazolide (crude product) (Example P48) is introduced into 6 ml of 1,2-dichloroethane at 22° C. After the addition of 0.21 ml of allylamine, the mixture is stirred overnight and then taken up in ethyl acetate and washed in succession with dilute sodium hydroxide solution, brine, dilute hydrochloric acid and brine. Drying over sodium sulfate, filtration and concentration by evaporation in vacuo yield 0.77 g of the desired compound in the form of a white solid having a melting point of 146-148° C.
Example P51: 3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-methanesulfanylmethyl)-[1H]-pyridin-2-one[0302] 96
[0303] 4.0 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol (Example P27) are introduced into a mixture of 40 ml of dry dimethoxyethane and 10 ml of dry dimethylformamide at 22° C., and 0.49 g of a 60% sodium hydride (NaH) dispersion in hexane is added. After 15 minutes' stirring, 2.12 g of lithium bromide are added and the mixture is subsequently stirred for 10 minutes. 2.0 ml of chlorodimethyl sulfide are then added and the mixture is further stirred overnight at 70° C. After cooling to 22° C., a sample is removed and analysed in a thin-layer chromatogram (TLC). Since starting material is still present, a further 0.30 g of sodium hydride dispersion (60%) and 0.60 ml of chlorodimethyl sulfide are added and the mixture is then again stirred overnight at 70° C. After cooling to 22° C., the mixture is taken up in ethyl acetate, and dilute hydrochloric acid is added carefully. After extraction by shaking, and separation of the phases, the ethyl acetate phase is washed with brine, dried over sodium sulfate, filtered and concentrated to dryness in vacuo. The crude product is purified over silica gel (eluant: n-hexane/ethyl acetate 2/1 (v/v)). First 0.51 g of the O-alkyl isomer is eluted and then 3.04 g of the desired title compound in the form of a yellow oil, which slowly crystallises out.
[0304] The Rf value of the title compound on silica gel 60 F254 (eluant: n-hexane/ethyl acetate/glacial acetic acid 20/20/1 (v/v/v)) is 0.37, the Rf value of the O-alkyl isomer is 0.70 and the Rf value of the starting material is 0.31.
Example P52: 3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-methanesulfonylmethyl)-[1H]-pyridin-2-one[0305] 97
[0306] 1.97 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-methanesulfanylmethyl)-[1H]-pyridin-2-one (Example P51) are introduced into 25 ml of dichloroethane at 22° C. 3.75 g of m-chloroperbenzoic acid (70%) are added to the yellow solution with a slight exothermic reaction. The mixture is stirred overnight at 22° C. The next day, the reaction mixture is taken up in ethyl acetate and washed with dilute sodium hydroxide solution and then with brine. After drying over sodium sulfate, filtration is carried out followed by concentration to dryness in vacuo. 2.05 g of the desired title compound are obtained in the form of a white solid having a melting point of 171-172° C.
Example P53: 3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5fluoro-1-methanesulfinylethyl)-[1H]-pyridin-2-one[0307] 98
[0308] 1.18 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-methanesulfanylethyl)-[1H]-pyridin-2-one are introduced into 7 ml of glacial acetic acid. After the addition of 0.27 g of hydrogen peroxide/urea adduct, the mixture is stirred overnight at 22° C. The next day, the reaction mixture is taken up in ethyl acetate and washed in succession with dilute sodium hydroxide solution, dilute hydrochloric acid and brine. After drying over sodium sulfate, the mixture is filtered and concentrated to dryness in vacuo. The residue (1.12 g of a yellow solid) is stirred with 10 ml of diethyl ether, and then filtered and washed with n-hexane. 1.05 g of the desired compound are obtained in the form of a white solid having a melting point of 143-145° C.
Example P54: 1-Benzyl-3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-[1H]-pyridine-2-thione[0309] 99
[0310] 0.50 g of 1-benzyl-3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-[1H]-pyridin-2-one is introduced into 5 ml of toluene, 0.63 g of Lawesson's reagent is added and the resulting yellow suspension is stirred overnight at 120° C. The next day, the mixture is cooled to 22° C., diluted with methylene chloride and, after the addition of 3 g of silica gel, concentrated to dryness in vacuo. The silica gel is applied to a flash chromatography column and eluted first with toluene/ethyl acetate 30/1 (v/v) and then with n-hexane/ethyl acetate 2/1 (v/v). 0.32 g of the desired title compound is obtained in the form of a yellow solid having a melting point of 135-138° C.
[0311] The Rf value of the starting material on silica gel 60 F254 (eluant: toluene/ethyl acetate 30/1 (v/v)) is 0.02 and the Rf value of the title compound is 0.18.
Example P55: 3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-propionaldehyde[0312] 100
[0313] 0.40 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-1-(2-[1.3]-dioxolan-2-ylethyl)-5-fluoro-[1H]-pyridin-2-one is stirred overnight at 22° C. in a mixture of 6 ml of 2N hydrochloric acid and 6 ml of diethyl ether. The next day, the same amount of the mixture together with 2 ml of tetrahydrofuran are added and the mixture is again stirred overnight. The mixture is subsequently diluted with diethyl ether and washed three times with brine, dried over sodium sulfate, filtered and concentrated to dryness in vacua. 0.23 g of the desired compound (crude) is obtained in the form of a yellow oil.
[0314] 1H-NMR (CDCl3): 9.73 ppm (s, 1H); 7.61 ppm (d, 1H); 6.73 ppm (t, 1H); 4.15 ppm (broad signal, 2H); 3.85 ppm (s, 3H); 2.98 ppm (t, 2H).
Example P56: 2-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-yloxy)-acetamide[0315] 101
[0316] 20.0 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol (Example P27) are placed together with 18.9 g of potassium carbonate and 6.4 g of chloroacetamide at 22° C. and the mixture is stirred overnight at 50° C. The next day, the mixture is cooled to 22° C. and then introduced into 2 liters of ice-water. After subsequently stirring for 10 minutes at 22° C., the resulting slurry is filtered. The filtration residue is washed with cold water and then dried in vacuo at 60° C. 20.2 g of the desired title compound are obtained in the form of a white solid having a melting point of 178-180° C.
Example P57: 3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ylamine[0317] 102
[0318] 7.1 g of potassium carbonate are introduced into 200 ml of dry N-methylpyrrolidone (NMP) and the mixture is heated to a temperature of 150° C. With stirring, 19.6 g of 2-(3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-yloxy)-acetamide (Example P56) are introduced in portions in the course of 2 hours and then the mixture is stirred for 10 hours at 150° C., subsequently cooled to 22° C. and partitioned between diethyl ether and water. After extraction by shaking, and separation of the phases, the ethereal phase is washed with brine, dried over sodium sulfate, filtered and concentrated together with twice the amount of silica gel. The silica gel is applied to a flash chromatography column and then elution is carried out with a n-hexane/ethyl acetate 1/1 (v/v) mixture. 9.3 g of the desired title compound having a melting point of 100-101° C. are obtained.
[0319] The Rf value of the starting material on silica gel 60 F254 (eluant: n-hexane/ethyl acetate 1/1 (v/v)) is 0.14 and the Rf value of the target compound is 0.43.
Example P58: 8-Chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-6-fluoroimidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester[0320] 103
[0321] 1.96 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ylamine (Example P57) are placed together with 1.25 ml of bromopyruvic acid ethyl ester (90%) in 20 ml of absolute ethanol. The mixture is stirred for 6 hours at 90 ° C. and then cooled to 22° C. and concentrated to dryness in vacuo. The residue is crystallised by the addition of diethyl ether and stirred, and n-hexane is added until precipitation is complete. The crystal fraction is filtered off, washed with n-hexane and dried in vacuo. 2.52 g of a yellowish-brown solid are obtained, which is dissolved in ethyl acetate and washed with dilute sodium hydrogen carbonate solution and then with brine. The organic phase is dried over sodium sulfate and then filtered and concentrated to dryness in vacuo. The residue obtained is digested in n-hexane, filtered, washed and dried. 1.88 g of the title compound are obtained in the form of a beige solid having a melting point of 140-143° C.
Example P59: 8-Chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-6-fluoroimidazo[1,2-a]pyridine-2-carboxylic acid[0322] 104
[0323] 0.51 g of 8-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-6-fluoroimidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester (Example P58) is dissolved in 3 ml of dimethyl sulfoxide and, with cooling in an ice-bath, 0.63 ml of a 2N aqueous sodium hydroxide solution is added. The mixture is then stirred for 1 hour at 22° C. Because the TLC analysis of a worked-up sample indicates that starting material is still present, a further 0.1 ml of 2N sodium hydroxide solution is added. After subsequently stirring for 30 minutes, the mixture is rendered strongly acidic with dilute hydrochloric acid, the resulting slurry is filtered, and the filtration residue is subsequently washed with cold water and dried in vacuo at 50° C. 0.35 g of the desired title compound is obtained in the form of a white solid (crude product).
Example P60: 8-Chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-6-fluoroimidazo[1,2-a]pyridin-2-yl)methanol[0324] 105
[0325] 0.56 g of 8-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-6-fluoroimidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester (Example P58) is introduced at 22° C. into 5 ml of diethyl ether and then treated with a total of 0.18 g of lithium aluminium hydride in portions with stirring. The resulting reddish-brown suspension is subsequently stirred for 1 hour and then first an excess of ethyl acetate and then dilute hydrochloric acid are added dropwise. The separated organic phase is washed with brine, filtered and concentrated to dryness in vacuo. 0.14 g of a yellowish-brown oil is obtained, which is purified over silica gel using ethyl acetate as eluant. 0.40 g of the desired compound is obtained in the form of a beige solid having a melting point of 152-153° C.
[0326] The preferred compounds listed in the following Tables can also be prepared in an analogous manner, and according to methods such as are illustrated in the general Reaction Schemes 1-3 and in the references quoted. 1 TABLE 1 A preferred group of compounds of formula I corresponds to the general 106 formula (I1), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I1.
[0327] 2 TABLE 2 Another preferred group of compounds of formula I corresponds to the general formula 107 (I2), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I2.
[0328] 3 TABLE 3 Another preferred group of compounds of formula I corresponds to the general formula 108 (I3), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I3.
[0329] 4 TABLE 4 Another preferred group of compounds of formula I corresponds to the general formula 109 (I4), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I4.
[0330] 5 TABLE 5 Another preferred group of compounds of formula I corresponds to the general formula 110 (I5), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I5.
[0331] 6 TABLE 6 Another preferred group of compounds of formula I corresponds to the general formula 111 (I6), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I6.
[0332] 7 TABLE 7 Another preferred group of compounds of formula I corresponds to the general formula 112 (I7), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I7.
[0333] 8 TABLE 8 Another preferred group of compounds of formula I corresponds to the general formula 113 (I8), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I8.
[0334] 9 TABLE 9 Another preferred group of forula I corresponds to the general formula 114 (I9), in which the sets of correlated substituents, R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I9.
[0335] 10 TABLE 10 Another preferred group of compounds of formula I corresponds to the general formula 115 (I10), in which the sets of correlated subtituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I10.
[0336] 11 TABLE 11 Another preferred group of compounds of formula I corresponds to the general formula 116 (I11), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I11.
[0337] 12 TABLE 12 Another preferred group of compounds of formula I corresponds to the general formula 117 (I12), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I12.
[0338] 13 TABLE 13 Another preferred group of compounds of formula I corresponds to the general formula 118 (I13), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I13.
[0339] 14 TABLE 14 Another preferred group of compounds of formula I corresponds to the general formula 119 (I14), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I14.
[0340] 15 TABLE 15 Another preferred group of compounds of formula I corresponds to the general formula 120 (I15), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I15.
[0341] 16 TABLE 16 Another preferred group of compounds of formula I corresponds to the general formula 121 (I16), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I16.
[0342] 17 TABLE 17 Another preferred group of compounds of formula I corresponds to the general formula 122 (I17), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I17.
[0343] 18 TABLE 18 Another preferred group of compounds of formula I corresponds to the general formula 123 (I18), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I18.
[0344] 19 TABLE 19 Another preferred group of compounds of formula I corresponds to the general formula 124 (I19), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I19.
[0345] 20 TABLE 20 Another preferred group of compounds of formula I corresponds to the general formula 125 (I20), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I20.
[0346] 21 TABLE 21 Another preferred group of compounds of formula I corresponds to the general formula 126 (I21), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific com- pounds of formula I21.
[0347] 22 TABLE 22 Another preferred group of compounds of formula I corresponds to the general formula 127 (I22), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific com- pounds of formula I22,
[0348] 23 TABLE 23 Another preferred group of compounds of formula I corresponds to the general formula 128 (I23), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific com- pounds of formula I23.
[0349] 24 TABLE 24 Another preferred group of compounds of formula I corresponds to the general formula 129 (I24), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific com- pounds of formula I24.
[0350] 25 TABLE 25 Another preferred group of compounds of formula I corresponds to the general formula 130 (I25), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific com- pounds of formula I25.
[0351] 26 TABLE 26 Another preferred group of compounds of formula I corresponds to the general formula 131 (I26), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific com- pounds of formula I26.
[0352] 27 TABLE 27 Another preferred group of compounds of formula I corresponds to the general formula 132 (I27), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific com- pounds of formula I27.
[0353] 28 TABLE 28 ANother preferred group of compounds of formula I corresponds to the general formula 133 X1 and R13 are given in Table A, thus disclosing 654 specific com- pounds of formula I28.
[0354] 29 TABLE 29 Another preferred group of compounds of formula I corresponds to the general formula 134 (I29), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific com- pounds of formula I29.
[0355] 30 TABLE 30 Another preferred group of compounds of formula I correspons to the general formula 135 (I30), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific com- pounds of formula I30.
[0356] 31 TABLE 31 Another preferred group of compounds of formula I corresponds to the general formula 136 (I31), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compound of formula I31.
[0357] 32 TABLE 32 Another preferred group of compounds of formula I corresponds to the general formula 137 (I32), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific com- pounds of formula I32.
[0358] 33 TABLE 33 Another preferred group of compounds of formula I corresponds to the general formula 138 (I33), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific com- pounds of formula I33.
[0359] 34 TABLE 34 Another preferred group of compounds of formula I corresponds to the general formula 139 (I34), in which the sets of correlated substituents R11, X1 and R13 are given in Table A, thus disclosing 654 specific com- pounds of formula I34.
[0360] 35 TABLE 35 Another preferred group of compounds of formula I corresponds to the general formula 140 (I35), in which the sets of correlated substitutents R11, X1 and R13 are given in Table A, thus disclosing 654 specific com- pounds of formula I35.
[0361] 36 TABLE 36 Another preferred group of compounds of formula I corresponds to the general formula 141 (I36) in which the sets of correlated substitutents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I36.
[0362] 37 TABLE 37 Another preferred group of compounds of formula I corresponds to the general formula 142 (I37), in which the sets of correlated substitutents R11, X1 and R13 are given in Table A, thus disclosing 654 specific compounds of formula I37.
[0363] 38 TABLE A Compd. No. R11 X1 R13 .001 H O CH3 .002 F O CH3 .003 Cl O CH3 .004 F O CH2CH3 .005 Cl O CH2CH3 .006 H O CH2CH3 .007 F O CH2CH2CH3 .008 Cl O CH2CH2CH3 .009 H O CH2CH2CH3 .010 F O CH2CH2CH2CH3 .011 Cl O CH2CH2CH2CH3 .012 F O CH2CH2CH2CH2CH3 .013 Cl O CH2CH2CH2CH2CH3 .014 F O CH2CH2CH2CH2CH2CH3 .015 F O CH2CH2CH(CH3)2 .016 Cl O CH2CH2CH(CH3)2 .017 H O CH2CH2CH(CH3)2 .018 F O CH2CH(CH3)CH2CH3 .019 Cl O CH2CH(CH3)CH2CH3 .020 H O CH2CH(CH3)CH2CH3 .021 F O CH2CH(CH3)CH2CH2CH3 .022 F O CH2CH2CH(CH3)CH2CH3 .023 F O CH2CH2CH2CH(CH3)2 .024 F O CH(CH3)CH2CH2CH2CH3 .025 Cl O CH(CH3)CH2CH2CH2CH3 .026 H O CH(CH3)CH2CH2CH2CH3 .027 F O CH2C(CH3)3 .028 Cl O CH2C(CH3)3 .029 H O CH2CH(CH3)2 .030 Cl O CH2CH(CH3)2 .031 F O CH2CH(CH3)2 .032 F O CH2C(CH3)2CH2CH3 .033 Cl O CH2C(CH3)2CH2CH3 .034 H O CH2C(CH3)2CH2CH3 .035 F O CH2CH2C(CH3)3 .036 Cl O CH2CH2C(CH3)2 .037 F O CH2CH2CHCH2 .038 Cl O CH2CH2CHCH2 .039 H O CH2CH2CHCH2 .040 F O CH2CH2CH2CHCH2 .041 Cl O CH2CH2CH2CHCH2 .042 H O CH2CH2CH2CHCH2 .043 F O CH2CH2CH2CH3 .044 F O CH(CH3)2 .045 F O CH2CF3 .046 Cl O CH2CF3 .047 H O CH2CF3 .048 F O CH2CHF2 .049 Cl O CH2CHF2 .050 F O CH2CH2CF3 .051 Cl O CH2CH2CF3 .052 F O CH2CCl3 .053 F O CH2CH2CF3 .054 Cl O CH2CH2CF3 .055 F O CH2CH2CHF2 .056 Cl O CH2CH2CHF2 .057 H O CH2CH2CHF2 .058 F O CH2CH2CH(OH)CH3 .059 F O CH2CH(OH)CH2CH3 .060 Cl O CH2CH(OH)CH2CH3 .061 F Cl CH2CH(OH)CH3 .062 H O CH2CH2CHClCH3 .063 Cl O CH2CH2CHClCH3 .064 F O CH2CH2CHClCH3 .065 F O CH2CH2CHFCH3 .066 F O CH2CHFCH2CH3 .067 Cl O CH2CHFCH2CH3 .068 H O CH2CHFCH2CH3 .069 F O CH2CHClCH2CH3 .070 F O CH2CH2F .071 Cl O CH2CH2F .072 F O CH2CH2Cl .073 F O CH2CH2Br .074 Cl O CH2CH2Cl .075 H O CH2CH2O .076 F O CH2CHF2 .077 F O CH2CHBr2 .078 H O CH2CHCH2 .079 Cl O CH2CHCH2 .080 F O CH2CHCH2 .081 F O CH2CH(CH3)CH2 .082 F O CH2CHCH(CH3) .083 F O CH2CHCH(Cl) (R-form) .084 Cl O CH2CHCH(Cl) (E-form) .085 H O CH2CHCH(Cl) (E-form) .086 F O CH2CHCH(Cl) (Z-form) .087 Cl O CH2CHCH(Cl) (Z-form) .088 H O CH2CH2OH .089 Cl O CH2CH2OH .090 F O CH2CH2OH .091 F O CH2CH2CH2OH .092 Cl O CH2CH2CH2OH .093 F O CH2CH(OH)CH3 .094 Cl O CH2CH(OH)CH3 .095 F O CH2CHCHCl .096 Cl O CH2CHCHCl .097 H O CH2CHCHCl ,098 H O CH2CCH .099 Cl O CH2CCH .100 F O CH2CCH .101 F O CH2CH(CH3)CCH .102 Cl O CH2CH2CCH .103 F O CH2CH2CCH .104 Cl O CH2CH2C6H5 .105 F O CH2CH2C6H5 .106 F O CH2CH2CH2C6H5 .107 F O CH2CH2CH(CH3)C6H5 .108 F O CH2CH2CH2CH2(p-F—C6H4) .109 H O CH2C6H5 .110 Cl O CH2C6H5 .111 F O CH2C6H5 .112 F O CH2(o-F—C6H4) .113 H O CH2(p-Cl—C6H4) .114 F O CH2(m-CF3—C6H4) .115 F O CH2(3,4-di-Cl—C6H3) .116 F O CH2(3,5-di-CH3—C6H3) .117 F O CH2CH2(2,6-di-F—C6H4) .118 Cl O CH2CH2(2,6-di-F—C6H3) .119 H O CH2CH2(2,6-di-F—C6H3) .120 F O CH2CH2CH2(4-F—C6H4) .121 Cl O CH2CH2CH2(4-F—C6H4) .122 F O CH2CH2CH(CH3)(4-CH3—C6H4) .123 Cl O CH2CH2CH(CH3)(4-CH3—C6H4) .124 H O CH2CN .125 Cl O CH2CN .126 F O CH2CN .127 F O CH2CHFCN .128 F O cyclopropyl .129 F O cyclopentyl .130 F O CH2-cyclpentyl .131 F O CH2-cyclopropyl .132 F O CH2CH2Cl .133 F O CH2CHCl2 .134 H O CH2OCH3 .135 Cl O CH2OCH3 .136 F O CH2OCH3 .137 F O CH2CH2OCH3 .138 Cl O CH2CH2OCH3 .139 H O CH2CH2OCH3 .140 F O CH2CH2OCH2CH3 .141 F O CH2CH(CH3)OCH3 .142 H O CH2CH2OCH2CH2OCH3 .143 Cl O CH2CH2OCH2CH2OCH3 .144 F O CH2CH2OCH2CH2OCH3 .145 H O CH2SCH3 .146 Cl O CH2SCH3 .147 F O CH2SCH3 .148 H O CH2S(O)CH3 .149 Cl O CH2S(O)CH3 .150 F O CH2S(O)CH3 .151 H O CH2S(O)2CH3 .152 Cl O CH2S(O)2CH3 .153 F O CH2S(O)2CH3 .154 F O CH2SCH2CH3 .155 F O CH2CH2SCH3 .156 F O CH2CH2SCH2CH3 .157 Cl O CH2CH2SCH2CH3 .158 H O CH2CH2SCH2CH3 .159 Cl O CH2CH2SCH3 .160 H O CH2CH2SCH3 .161 F O CH2CH2S(O)CH3 .162 F O CH2CH2S(O)2CH3 .163 Cl O CH2CH2S(O)CH3 .164 Cl O CH2CH2S(O)2CH3 .165 F O CH2CH2S(O)CH2CH3 .166 Cl O CH2CH2S(O)CH2CH3 .167 H O CH2CH2S(O)CH2CH3 .168 F O CH2CH2S(O)2CH2CH3 .169 Cl O CH2CH2S(O)2CH2CH3 .170 H O CH2CH2S(O)2CH2CH3 .171 F O CH2CH2CH2SCH3 .172 F O CH2CH2CH2S(O)CH3 .173 F O CH2CH2CH2S(O)2CH3 .174 F O CH2CH(CH3)SCH3 .175 H O CH2COOH .176 Cl O CH2COOH .177 F O CH2COOH .178 F O CH2COOCH3 .179 H O CH2COOCH2CH3 .180 Cl O CH2COOCH2CH3 .181 F O CH2COOCH2CH3 .182 F O CH2COOCH(CH3)2 .183 Cl O CH2COOCH(CH3)2 .184 H O CH2COOCH(CH3)2 .185 F O CH2COOCH(CH2CH3)2 .186 Cl O CH2COOCH(CH3)CH2CH3 .187 F O CH2COOCH2CH2CH3 .188 F O CH2COOCH2CH2CH2CH3 .189 F O CH2COOCH2CH(CH3)2 .190 F O CH2COOC(CH3)2 .191 F O CH2COOCH2CHCH2 .192 F O CH2COOCH2CCH .193 Cl O CH2COOCH2CCH .194 H O CH2COOCH2CCH .195 F O CH2COOCH2C6H5 .196 F O CH2COOCH2(o-F—C6H4) .197 F O CH2COOCH2(p-Cl—C6H4) .198 F O CH2COOCH2(m-CH3—C6H4) .199 F O CH2COOCH2(2,4-di-CH3—C6H3) .200 Cl O CH2COOCH2(2,4-di-CH3—C6H3) .201 F O CH2CH2COOCH2(3,4-di-Cl—C6H3) .202 F O CH2CH2CH2COOH .203 Cl O CH2CH2CH2COOH .204 F O CH2CH2CH2COOCH3 .205 F O CH2CH2CH2COOCH2CH3 .206 Cl O CH2CH2CH2COOCH2CH3 .207 F O CH2CH2CH2CH2COOH .208 F O CH2CH2CH2CH2COOCH3 .209 Cl O CH2CH2CH2CH2COOCH3 .210 H O CH2CH2CH2CH2COOCH3 .211 H O CH2CHO .212 Cl O CH2CHO .213 F O CH2CHO .214 H O CH2C(O)CH3 .215 Cl O CH2C(O)CH3 .216 F O CH2C(O)CH3 .217 F O CH2C(O)SCH3 .218 Cl O CH2C(O)CSCH3 .219 F O CH2C(O)SCH2CH2CH3 .220 Cl O CH2C(O)SCH2CH2CH3 .221 F O CH2C(O)SCH2CHCH2 .222 Cl O CH2C(O)SCH2CHCH2 .223 F O CH2COSCH2CH3 .224 H O CH2COSCH(CH3)2 .225 Cl O CH2COSCH(CH3)2 .226 F O CH2COSCH(CH3)2 .227 F O CH2COSCH2C6H5 .228 Cl O CH2COSCH2C6H5 .229 H O CH2COSCH2C6H5 .230 F O CH2CONH2 .231 F O CH2CONH(CH3) .232 F O CH2CON(CH3)2 .233 Cl O CH2CON(CH3)2 .234 F O CH2CON(CH2CH3)2 .235 Cl O CH2CON(CH2CH3)2 .236 H O CH2CON(CH2CH3)2 .237 F O CH2CON(CH2CH3)(CH3) .238 F O CH2CON(CH2CH2CH3)2 .239 Cl O CH2CON(CH2CH2CH3)2 .240 H O CH2CONH(CH2CH2CH3) .241 F O CH2CONH(CH2CH2CH3) .242 H O CH2CONHCH3CHCH2 .243 Cl O CH2CONHCH2CHCH2 .244 F O CH2CONHCH2CHCH2 .245 H O CH2CONHCH2CCH .246 Cl O CH2CONHCH2CCH .247 F O CH2CONHCH2CCH .248 F O CH2CONHC6H5 .249 Cl O CH2CONHC6H5 .250 F O CH3CONH(3,4-di-Cl—C6H3) .251 F O CH2CON(CH3)(C6H5) .252 Cl O CH2CON(CH3)(C6H5) .253 F O CH2CONH(o-F—C6H4) .254 F O CH2CONHCH2(C6H5) .255 Cl O CH2CONHCH2(C6H5) .256 H O CH2CONHCH2(C6H5) .257 F O CH2CON(CH3)CH2(C6H5) .258 F O CH2CONH(3,4-di-Cl—C6H3) .259 Cl O CH2CONH(3,4-di-Cl—C6H3) .260 F O CH2CONHCH2(4-Cl—C6H4) .261 Cl O CH2CONHCH2(4-Cl—C6H4) .262 F O CH2CON(CH3)CH2(4-Cl—C6H4) .263 F O CH2CON(CH2CH3)CH2(4-Cl—C6H4) .264 Cl O CH2CON(CH2CH3)CH2(4-Cl—C6H4) .265 F O CH2CON(CH2CHCH2)CH2(4-Cl—C6H4) .266 Cl O CH2CON(CH2CHCH2)CH2(4-Cl—C6H4) .267 H O CH2CH2COOH .268 Cl O CH2CH2COOH .269 F O CH2CH2COOH .270 F O CH2CH2COOCH2CH3 .271 Cl O CH2CH2COOCH2CH3 .272 H O CH2CH2COOCH2CH3 .273 F O CH2CH2COOCH2CHCH2 .274 Cl O CH2CH2COOCH2CHCH2 .275 F O CH2CH2COOCH2(C6H5) .276 F O CH2CH2COOCH(CH3)2 .277 Cl O CH2CH2COOCH(CH3)2 .278 H O CH2CH2CN .279 Cl O CH2CH2CN .280 F O CH2CH2CN .281 F O CH2CH(CH3)CN .282 Cl O CH2CH(CH3)CN .283 H O CH2CH(CH3)CN .284 F O CH2CH(Cl)CN .285 Cl O CH2CH(Cl)CN .286 F O CH2CH2CH2CN .287 Cl O CH2CH2CH2CN .288 F O CH2CH2CH(CH3)CN .289 F O CH2CH(CH3)CH2CN .290 Cl O CH2CH(CH3)CHO .291 Cl O CH(CH3)CH2CN .292 H O CH2CH2CHO .293 Cl O CH2CH2CHO .294 F O CH2CH2CHO .295 F O CH2CH(Cl)CHO .296 Cl O CH2CH(Cl)CHO .297 F O CH2CH(CH3)CHO .298 Cl O CH2CH(CH3)CHO .299 H O CH2CH(CH3)CHO .300 F O CH2CH2C(O)CH3 .301 Cl O CH2CH2C(O)CH3 .302 F O CH2COCH2CH3 .303 Cl O CH2COCH2CH3 .304 H O CH2COCH2CH3 .305 F O CH2COCH2CH2CH3 .306 F O CH2CH2COCH2CH3 .307 F O CH2CH2COCH2CH3 .308 F O CH2CH(CH3)COOH .309 Cl O CH2CH(CH3)COOH .310 H O CH2CH(CH3)COOH .311 F O CH2CH(CH3)COOCH3 .312 F O CH2CH(CH3)COOCH2CH3 .313 Cl O CH2CH(CH3)COOCH2CH3 .314 F O CH2CH2CH2COOH .315 Cl O CH2CH2CH2COOH .316 Cl O CH2CH2CH2COOCH3 .317 F O CH2CH2CH2COOCH3 .318 F O CH2CH2CH2COSCH2CH3 .319 F O CH2CH2CH2CONHCH2CCH .320 F O CH2CH2CH2CON(CH3)(CH2CCH) .321 F O CH2CH2CH2CON(CH3)2 .322 F O CH2CH2CH(CH3)COOCH2CH3 .323 H O CH2CH(OH)COOH .324 Cl O CH2CH(OH)COOH .325 F O CH2CH(OH)COOH .326 H O CH2CH(Cl)COOH .327 Cl O CH2CH(Cl)COOH .328 F O CH2CH(Cl)COOH .329 Cl O CH2CH(Cl)COOCH2CH3 .330 F O CH2CH(Cl)COOCH2CH3 .331 F O CH2CH(Cl)COOCH2(4-Cl—C6H4) .332 F O CH2CH(Cl)COOCH2CHCH2 .333 Cl O CH2CH(Cl)COOCH2CHCH2 .334 F O CH2CH(Cl)COOC(CH3)3 .335 Cl O CH2CH(Cl)COOCH(CH3)3 .336 F O CH2CH(Cl)COOCH2CH2CH3 .337 F O CH2C(CH3)(Cl)COOH .338 Cl O CH2C(CH3)(Cl)COOH .339 H O CH2C(CH3)(Cl)COOH .340 F O CH2CH(Cl)COOCH2CHCH2 .341 Cl O CH2CH(Cl)COOCH2CHCH2 .342 H O CH2CH(Cl)COOCH2CHCH2 .343 F O CH2CH(Cl)COOCH2CCH .344 F O CH2CH(Cl)COOCH2C6H5 .345 F O CH2CH(Br)COOH .346 Cl O CH2CH(Br)COOH .347 H O CH2CH(Br)COOH .348 F O CH2CH(Br)COOCH3 .349 Cl O CH2CH(Br)COOCH3 .350 F O CH2CH(Br)COOCH2CH3 .351 F O CH2CH(Br)COOCH2CHCH2 .352 Cl O CH2CH(Br)COOCH2CHCH2 .353 F O CH2CH(Br)COOCH2CCH .354 Cl O CH2CH(Br)COOCH2CCH .355 F O CH2CHBrCOOC(CH3)3 .356 Cl O CH2CHBrCOOC(CH3)3 .357 F O CH2CH(Cl)C(O)SCH(CH3)2 .358 F O CH2CH(Cl)C(O)NH2 .359 Cl O CH2CH(Cl)C(O)NH2 .360 F O CH2CH(Cl)C(O)NH(CH2CCH) .361 Cl O CH2CH(Cl)C(O)NH(CH2CCH) .362 F O CH2CH(Cl)C(O)NH(CH2CHCH2) .363 F O CH2CH(Cl)C(O)N(CH2CH3)(CH2CHCH2) .364 Cl O CH2CH(Cl)C(O)N(CH2CH3)(CH2CHCH2) .365 F O CH2CH(CH3)C(O)N(CH3)(CH2CHCH2) .366 F O CH2COOCH2CH2Cl .367 F O CH2COOCH2CF3 .368 Cl O CH2COOCH2CF3 .369 H O CH2COOCH2CF3 .370 F O CH2COOCH2CH2F .371 Cl O CH2COOCH2CH2F .372 F O CH2COOCH2CH2Cl .373 Cl O CH2COOCH2CH2Cl .374 F O CH2COOCH2CH2CH2Cl .375 F O CH2COOCH2CH(Cl)CH3 .376 Cl O CH2COOCH2CH(Cl)CH3 .377 F O CH2COOCH2CH(F)CH3 .378 Cl O CH2COOCH2CH(F)CH3 .379 H O 143 .380 H O 144 .381 Cl O 145 .382 Cl O 146 .383 F O 147 .384 F O 148 .385 F O S(O)2CH3 .386 F O S(O)2CH2CH3 .387 Cl O S(O)2CF3 .388 Cl O S(O)2CH2CH3 .389 F O S(O)2CH(CH3)2 .390 H O C(O)CH3 .391 Cl O C(O)CH3 .392 F O C(O)CH3 .393 F O C(O)CF3 .394 F O C(O)CH2CH3 .395 H O OH .396 Cl O OH .397 F O OH .398 H O OCH3 .399 Cl O OCH3 .400 F O OCH3 .401 H O OCH2CH3 .402 Cl O OCH2CH3 .403 F O OCH2CH3 .404 F O OCH2CH(CH3)2 .405 F O OCH2C(CH3)3 .406 F O OCF3 .407 F O OCHF2 .408 F O OCH2CHCH2 .409 F O OCH2C(CH3)CH2 .410 F O OCH2CHCHCl .411 H O OCH2OCH3 .412 Cl O OCH2OCH3 .413 F O OCH2OCH3 .414 H O OCH2SCH3 .415 Cl O OCH2SCH3 .416 F O OCH2SCH3 .417 F O OCH2CCH .418 H O OCH2COOH .419 Cl O OCH2COOH .420 F O OCH2COOH .421 F O OCH2COOCH3 .422 F O OCH2COOCH2CH3 .423 F O OCH2COOCH(CH3)2 .424 H O OCH(CH3)COOH .425 Cl O OCH(CH3)COOH .426 F O OCH(CH3)COOH .427 F O OCH(CH3)COOCH2CH3 .428 F O OCH(CH3)COOCH2CCH .429 F O OCH(CH3)COOCH2CHCH2 .430 F O OCH2COSCH2CH3 .431 H O OCH2COSCH(CH3)2 .432 Cl O OCH2COSCH(CH3)2 .433 F O OCH2COSCH(CH3)2 .434 F O OCH2COSCH2C6H5 .435 F O OCH2CONH2 .436 F O OCH2CON(CH3)2 .437 H O OCH2CONHCH2CCH .438 Cl O OCH2CONHCH2CCH .439 F O OCH2CONHCH2CCH .440 F O OCH2C6H5 .441 F O OCH2(p-CH3O—C6H4) .442 F O OCH2(o-F—C6H4) .443 Cl O OCH2(m-CF3—C6H4) .444 F O OCH2CH2C6H5 .445 H O OCH2CN .446 H O OCH2CH2Cl .447 Cl O OCH2CN .448 Cl O OCH2CH2Cl .449 F O OCH2CN .450 F O OCH2CH2Cl .451 F O OCH2CH2CF3 .452 H O OCH2CH2OH .453 Cl O OCH2CH2OH .454 F O OCH2CH2OH .455 H O OCH2CH2CN .456 Cl O OCH2CH2CN .457 F O OCH2CH2CN .458 F O OCH2CH(OH)(C6H5) .459 F O OCH2CH(OH)(CH3) .460 Cl O OCH2CH(OCH3)(CH3) .461 F O OCH2CH(OCH3)(CH3) .462 H O OC(O)CH3 .463 Cl O OC(O)CH3 .464 F O OC(O)CH3 .465 H S CH3 .466 Cl S CH3 .467 F S CH3 .468 H S CH2CH3 .469 Cl S CH2CH3 .470 F S CH2CH3 .471 F S CH2CH2CH3 .472 F S CH2CH(CH3)2 .473 F S CH2CH2CF3 .474 F S CH(CH3)2 .475 F S CH2CH(CH3)2 .476 F S CH2CH(Cl)CH3 .477 F S CH2CH2CH(Cl)CH3 .478 F S CH2CH2CH(OH)CH3 .479 H S CH2CHCH2 .480 Cl S CH2CHCH2 .481 F S CH2CHCH2 .482 F S CH2C(CH3)CH2 .483 H S CH2CCH .484 Cl S CH2CCH .485 F S CH2CCH .486 F S CH2CH2CCH .487 F S CH(CH3)CCH .488 H S CH2CH2OH .489 Cl S CH2CH2OH .490 F S CH2CH2OH .491 F S CH2CH(OH)CH3 .492 H S CH2C6H5 .493 Cl S CH2C6H5 .494 F S CH2C6H5 .495 Cl S CH2(o-F—C6H4) .496 F S CH2(o-F—C6H4) .497 F S CH2(m-CF3—C6H4) .498 F S CH2(p-CH3—C6H4) .499 F S CH2(2,4-di-F—C6H3) .500 F S CH2CH2CH(CH3)C6H5 .501 F S CH2CH2CH2CH2(p-F—C6H4) .502 Cl S CH2CN .503 F S CH2CN .504 F S cyclopropyl .505 Cl S CH2-cyclopropyl .506 F S CH2-cyclopropyl .507 F S CH2Cl .508 H S CH2OCH3 .509 Cl S CH2OCH3 .510 F S CH2OCH3 .511 F S CH2OCH2CHCH2 .512 F S CH2CH2OCH3 .513 F S CH2CH(OCH3)CH3 .514 F S CH2CH(OCH2CCH)CH3 .515 H S CH2CH2OCH2CH2OCH3 .516 Cl S CH2CH2OCH2CH2OCH3 .517 F S CH2CH2OCH2CH2OCH3 .518 H S CH2SCH3 .519 Cl S CH2SCH3 .520 F S CH2SCH3 .521 F S CH2SCH2CHCH2 .522 F S CH2SCH2CCH .523 F S CH2CH2SCH3 .524 F S CH2CH2S(O)CH3 .525 F S CH2CH2S(O)2CH3 .526 H S CH2COOH .527 Cl S CH2COOH .528 F S CH2COOH .529 F S CH2COOCH3 .530 F S CH2COOCH2CH3 .531 F S CH2COOC(CH3)3 .532 F S CH2COOCH2C6H5 .533 F S CH2COOCH2(p-Cl—C6H4) .534 F S CH2C(O)SCH3 .535 H S CH2C(O)SCH(CH3)2 .536 Cl S CH2C(O)SCH(CH3)2 .537 F S CH2C(O)SCH(CH3)2 .538 F S CH2C(O)SCH2C6H5 .539 F S CH2C(O)NH2 .540 F S CH2C(O)NH(CH3) .541 F S CH2C(O)NH(CH2CCH) .542 F S CH2C(O)NH(CH2CCH) .543 F S CH2C(O)N(CH2CH3)2 .544 H S CH2CHO .545 Cl S CH2CHO .546 F S CH2CHO .547 F S CH2C(O)CH3 .548 H S CH2CH2COOH .549 Cl S CH2CH2COOH .550 F S CH2CH2COOH .551 H S CH2CH2CN .552 Cl S CH2CH2CN .553 F S CH2CH2CN .554 F S CH2CH2COOCH3 .555 F S CH2CH2COOCH2C6H5 .556 Cl S CH2CH2C(O)SCH2CH3 .557 F S CH2CH2C(O)SCH2CH3 .558 H S CH2CH(OH)COOH .559 Cl S CH2CH(OH)COOH .560 F S CH2CH(OH)COOH .561 H S CH2CH(Cl)COOH .562 Cl S CH2CH(Cl)COOH .563 F S CH2CH(Cl)COOH .564 Cl S CH2CH(Cl)COOCH2CH3 .565 F S CH2CH(Cl)COOCH2CH3 .566 F S CH2CH(Cl)COOH .567 F S CH2C(CH3)(Cl)COOH .568 F S CH2CH(Cl)COOCH2CHCH2 .569 Cl S CH2CH(Cl)COOCH2CCH .570 F S CH2CH(Cl)COOCH2CCH .571 F S CH2CH(Cl)COOCH2C6H5 .572 Cl S CH2CH(Br)COOH .573 F S CH2CH(Br)COOH .574 Cl S CH2CH(Cl)C(O)SCH(CH3)2 .575 F S CH2CH(Cl)C(O)SCH(CH3)2 .576 F S CH2CH(Cl)C(O)NH(CH2CCH) .577 F S CH2CH(CH3)C(O)N(CH3)(CH2CHCH2) .578 F S CH2CH2C(O)NH(CH2CCH) .579 H S 149 .580 Cl S 150 .581 F S 151 .582 H S 152 .583 Cl S 153 .584 F S 154 .585 H S OH .586 Cl S OH .587 F S OH .588 H S OCH3 .589 Cl S OCH3 .590 F S OCH3 .591 F S OCH2CH3 .592 Cl S OCH2CH(CH3)2 .593 F S OCH2CH(CH3)2 .594 F S OCH(CH3)2 .595 F S OCF3 .596 H S OCH2OCH3 .597 Cl S OCH2OCH3 .598 F S OCH2OCH3 .599 H S OCH2SCH3 .600 Cl S OCH2SCH3 .601 F S OCH2SCH3 .602 Cl S OCH2CHCH2 .603 F S OCH2CHCH2 .604 H S OCH2CCH .605 Cl S OCH2CCH .606 F S OCH2CCH .607 F S OCH(CH3)CHCH2 .608 F S OCH(CH3)CCH .609 F S OCH2CH2Cl .610 F S OCH2CH2CF3 .611 F S OCH2CHCH(Cl) .612 H S OCH2CHO .613 H S OCH2CHO .614 H S OCH2CHO .615 H S OCH2COOH .616 Cl S OCH2COOH .617 F S OCH2COOH .618 H S OCH2COOCH2CH3 .619 Cl S OCH2COOCH2CH3 .620 F S OCH2COOCH2CH3 .621 F S OCH(CH3)COOH .622 F S OCH(CH3)COOCH2CH3 .623 F S OCH(CH3)COOCH2CCH .624 F S OCH2C(O)NH2 .625 F S OCH2C(O)NH(CH3) .626 F S OCH2C(O)N(CH2CH3)2 .627 F S OCH2C(O)NH(CH2CCH) .628 Cl S OCH2C(O)N(CH3)2 .629 F S OCH2C(O)N(CH3)2 .630 F S OCH2C(O)N(CH3)(CH2(o-F—C6H4)) .631 Cl S OCH2C(O)SCH3 .632 F S OCH2C(O)SCH3 .633 F S OCH2C(O)SCH2CH3 .634 H S OCH2C(O)SCH(CH3)2 .635 Cl S OCH2C(O)SCH(CH3)2 .636 F S OCH2C(O)SCH(CH3)2 .637 Cl S OCH2C(O)SCH2C6H5 .638 F S OCH(CH3)C(O)SCH2C6H5 .639 H S OCH2CH2OH .640 Cl S OCH2CH2OH .641 F S OCH2CH2OH .642 H S OCH2CH(CH3)OH .643 Cl S OCH2CH(CH3)OH .644 F S OCH2CH(CH3)OH .645 F S OCH2CH2Cl .646 F S OCH2CF3 .647 Cl S OCH2CN .648 F S OCH2CN .649 H S OCH2CH2CM .650 Cl S OCH2CH2CN .651 F S OCH2CH2CN .652 Cl S OCH2CH2CF3 .653 F S OCH2CH2CF3 .654 F S OCH2CH(OH)(C6H5)
[0364] 39 TABLE 38 A preferred group of compounds of formula I corresponds to the general formula 155 (I38), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific compounds of formula I38.
[0365] 40 TABLE 39 Another preferred group of compounds of formula I corresponds to the general formula 156 (I39), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific compounds of formula I39.
[0366] 41 TABLE 40 Another preferred group of compounds of formula I corresponds to the general formula 157 (I40), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I40.
[0367] 42 TABLE 41 Another preferred group of compounds of formula I corresponds to the general formula 158 (I41), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I41.
[0368] 43 TABLE 42 Another preferred group of compounds of formula I corresponds to the general formula 159 (I42), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I42.
[0369] 44 TABLE 43 Another preferred group of compounds of formula I corresponds to the general formula 160 (I43), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I43.
[0370] 45 TABLE 44 Another preferred group of compounds of formula I corresponds to the general formula 161 (I44), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I44.
[0371] 46 TABLE 45 Another preferred group of compounds of formula I corresponds to the general formula 162 (I45), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I45.
[0372] 47 TABLE 46 Another preferred group of compounds of formula I corresponds to the general formula 163 (I46), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I46.
[0373] 48 TABLE 47 Another preferred group of compounds of formula I corresponds to the general formula 164 (I47), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I47.
[0374] 49 TABLE 48 Another preferred group of compounds of formula I corresponds to the general formula 165 (I48), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I48.
[0375] 50 TABLE 49 Another preferred group of compounds of formula I corresponds to the general formula 166 (I49), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I49.
[0376] 51 TABLE 50 Another preferred group of compounds of formula I corresponds to the general formula 167 (I50), in which the sets of correlated substituents R11, R12 and R13 are given in Table B, thus disclosing 264 specific com- pounds of formula I50.
[0377] 52 TABLE 51 Another preferred group of compounds of formula I corresponds to the general formula 168 (I51), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I51.
[0378] 53 TABLE 52 Another preferred group of compounds of formula I corresponds to the general formula 169 (I52), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I52.
[0379] 54 TABLE 53 Another preferred group of compounds of formula I corresponds to the general formula 170 (I53), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I53.
[0380] 55 TABLE 54 Another preferred group of compounds of formula I corresponds to the general formula 171 (I54), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I54.
[0381] 56 TABLE 55 Another preferred group of compounds of formula I corresponds to the general formula 172 (I55), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I55.
[0382] 57 TABLE 56 Another preferred group of compounds of formula I corresponds to the general formula 173 (I56), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I56.
[0383] 58 TABLE 57 Another preferred group of compounds of formula I corresponds to the general formula 174 (I57), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula R57.
[0384] 59 TABLE 58 Another preferred group of compounds of formula I corresponds to the general formula 175 (I58), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I58.
[0385] 60 TABLE 59 Another preferred group of compounds of formula I corresponds to the general formula 176 (I59), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I59.
[0386] 61 TABLE 60 Another preferred group of compounds of formula I corresponds to the general formula 177 (I60), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I50.
[0387] 62 TABLE 61 Another preferred group of compounds of formula I corresponds to the general formula 178 (I61), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I61.
[0388] 63 TABLE 62 Another preferred group of compounds of formula I corresponds to the general formula 179 (I62), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I62.
[0389] 64 TABLE 63 Another preferred group of compounds of formula I corresponds to the general formula 180 (I63), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I63.
[0390] 65 TABLE 64 Another preferred group of compounds of formula I corresponds to the general formula 181 (I64), in which the sets of correlated substitutents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I64.
[0391] 66 TABLE 65 Another preferred group of compounds of formula I corresponds to the general formula 182 (I65), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I65.
[0392] 67 TABLE 66 Another preferred group of compounds of formula I corresponds to the general formula 183 (I66), in which the sets of correlated substitutents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I66.
[0393] 68 TABLE 67 Another preferred group of compounds of formula I corresponds to the general formula 184 (I67), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I67.
[0394] 69 TABLE 68 Another preferred group of compounds of formula I corresponds to the general formula 185 (I68), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I68.
[0395] 70 TABLE 69 ANother preferred group of compounds of formula I corresponds to the general formula 186 (I69), in which the sets of correlated substitutents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I69.
[0396] 71 TABLE 70 Another preferred group of compounds of formula I corresponds to the general formula 187 (I70), in which the sets of forrelated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I70.
[0397] 72 TABLE 71 Another preferred group of compounds of formula I corresponds to the general formula 188 (I71), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I71.
[0398] 73 TABLE 70 Another preferred group of compounds of formula I corresponds to the general formula 189 (I72), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I72.
[0399] 74 TABLE 73 Another preferred group of compounds of formula I corresponds to the general formula 190 (I73), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I73.
[0400] 75 TABLE 74 Another preferred group of compounds of formula I corresponds to the general formula 191 (I74), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I74.
[0401] 76 TABLE 75 Another preferred group of compounds of formula I corresponds to the general formula 192 (I75), in which the sets of correlated substituents R11, R12 and R32 are given in table B, thus disclosing 264 specific com- pounds of formula I75.
[0402] 77 TABLE 76 Another group of compounds of formula I corresponds to the general formula 193 (I76), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I76.
[0403] 78 TABLE 77 Another preferred group of compounds of formula I corresponds to the general formula 194 (I77), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I78.
[0404] 79 TABLE 78 Another preferred group of compounds of formula I corresponds to the general formula 195 (I78), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I78.
[0405] 80 TABLE 79 Another preferred group of compounds of formula I corresponds to the general formula 196 (I79), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I79.
[0406] 81 TABLE 80 Another preferred Group of compounds of formula I corresponds to the general formula 197 (I80), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I80.
[0407] 82 TABLE 81 Another preferred group of compounds of formula I corresponds to the general formula 198 (I81), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I81.
[0408] 83 TABLE 82 Another preferred group of compounds of formula I corresponds to the genEral formula 199 (I82), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I82.
[0409] 84 TABLE 83 Another preferred group of compounds of formula I corresponds to the general formula 200 (I83), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I83.
[0410] 85 TABLE 84 Another preferred group of compounds of formula I corresponds to the general formula 201 (I84), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I84.
[0411] 86 TABLE 85 Another preferred group of compounds of formula I corresponds to the general formula 202 (I85), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I85.
[0412] 87 TABLE 86 Another prefered group of compounds of formula I corresponds to the general formula 203 (I86), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I86.
[0413] 88 TABLE 87 Another preferred group of compounds of formula I corresponds to the general formula 204 (I87) in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I87.
[0414] 89 TABLE 88 Another preferred group of compounds of formula I corresponds to the general formula 205 (I88), in which the sets of correlated substituents R11, R12 and R32 are given in Table B, thus disclosing 264 specific com- pounds of formula I88.
[0415] 90 TABLE B Compd. No. R11 R12 R32 or R34 .001 H Cl H .002 Cl Cl H .003 F Cl H .004 H Br H .005 Cl Br H .006 F Br H .007 Cl CF3 H .008 F CF3 H .009 F CH3 H .010 F OCF3 H .011 H Cl CH3 .012 Cl Cl CH3 .013 F Cl CH3 .014 H Br CH3 .015 Cl Br CH3 .016 F Br CH3 .017 Cl CF3 CH3 .018 F CF3 CH3 .019 F CH3 CH3 .020 F OCF3 CH3 .021 H Cl CH2CHCH2 .022 Cl Cl CH2CHCH2 .023 F Cl CH2CHCH2 .024 H Br CH2CHCH2 .025 Cl Br CH2CHCH2 .026 F Br CH2CHCH2 .027 Cl CF3 CH2CHCH2 .028 F CF3 CH2CHCH2 .029 F CH3 CH2CHCH2 .030 F OCF3 CH2CHCH2 .031 H Cl CH2CH(CH3)2 .032 Cl Cl CH2CH(CH3)2 .033 F Cl CH2CH(CH3)2 .034 H Br CH2CH(CH3)2 .035 Cl Br CH2CH(CH3)2 .036 F Br CH2CH(CH3)2 .037 Cl CF3 CH2CH(CH3)2 .038 F CF3 CH2CH(CH3)2 .039 F CH3 CH2CH(CH3)2 .040 F OCF3 CH2CH(CH3)2 .041 H Cl CH2CCH .042 Cl Cl CH2CCH .043 F Cl OH2CCH .044 H Br CH2CCH .045 Cl Br CH2CCH .046 F Br CH2CCH .047 Cl CF3 CH2CCH .048 F CF3 CH2CCH .049 F CH3 CH2CCH .050 F OCF3 CH2CCH .051 H Cl CF3 .052 Cl Cl CF3 .053 F Cl CF3 .054 H Br CF3 .055 Cl Br CF3 .056 F Br CF3 .057 Cl CF3 CF3 .058 F CF3 CF3 .059 F CH3 CF3 .060 F OCF3 CF3 .061 H Cl CH2Cl .062 Cl Cl CH2Cl .063 F Cl CH2Cl .064 H Br CH2Cl .065 Cl Br CH2Cl .066 F Br CH2Cl .067 Cl CF3 CH2Cl .068 F CF3 CH2Cl .069 F CH3 CH2Cl .070 F OCF3 CH2Cl .071 H Cl CH2CN .072 Cl Cl CH2CN .073 F Cl CH2CN .074 H Br CH2CN .075 Cl Br CH2CN .076 F Br CH2CN .077 Cl CF3 CH2CN .078 F CF3 CH2CN .079 F CH3 CH2CN .080 F OCF3 CH2CN .081 H Cl CH2OH .082 Cl Cl CH2OH .083 F Cl CH2OH .084 H Br CH2OH .085 Cl Br CH2OH .086 F Br CH2OH .087 Cl CF3 CH2OH .088 F CF3 CH2OH .089 F CH3 CH2OH .090 F OCF3 CH2OH .091 H Cl CH2OC(O)CH3 .092 Cl Cl CH2OC(O)CH3 .093 F Cl CH2OC(O)CH3 .094 H Br CH2OC(O)CH3 .095 Cl Br CH2OC(O)CH3 .096 F Br CH2OC(O)CH3 .097 Cl CF3 CH2OC(O)CH3 .098 F CF3 CH2OC(O)CH3 .099 F CH3 CH2OC(O)CH3 .100 F OCF3 CH2OC(O)CH3 .101 H Cl CH2OCH2CHCH2 .102 Cl Cl CH2OCH2CHCH2 .103 F Cl CH2OCH2CHCH2 .104 H Br CH2OCH2CHCH2 .105 Cl Br CH2OCH2CHCH2 .106 F Br CH2OCH2CHCH2 .107 Cl CF3 CH2OCH2CHCH2 .108 F CF3 CH2OCH2CHCH2 .109 F CH3 CH2OCH2CHCH2 .110 F OCF3 CH2OCH2CHCH2 .111 H Cl COOH .112 Cl Cl COOH .113 F Cl COOH .114 H Br COOH .115 Cl Br COOH .116 F Br COOH .117 Cl CF3 COOH .118 F CF3 COOH .119 F CH3 COOH .120 F OCF3 COOH .121 H Cl COOCH3 .122 Cl Cl COOCH3 .123 F Cl COOCH3 .124 H Br COOCH3 .125 Cl Br COOCH3 .126 F Br COOCH3 .127 Cl CF3 COOCH3 .128 F CF3 COOCH3 .129 F CH3 COOCH3 .130 F OCF3 COOCH3 .131 H Cl COOCH2CH3 .132 Cl Cl COOCH2CH3 .133 F Cl COOCH2CH3 .134 H Br COOCH2CH3 .135 Cl Br COOCH2CH3 .136 F Br COOCH2CH3 .137 Cl CF3 COOCH2CH3 .138 F CF3 COOCH2CH3 .139 F CH3 COOCH2CH3 .140 F OCF3 COOCH2CH3 .141 Cl Cl COOCH(CH3)2 .142 F Cl COOCH(CH3)2 .143 H Br COOCH(CH3)2 .144 Cl Br COOCH(CH3)2 .145 F Br COOCH(CH3)2 .146 Cl CF3 COOCH(CH3)2 .147 F CF3 COOCH(CH3)2 .148 F CH3 COOCH(CH3)2 .149 F OCF3 COOCH(CH3)2 .150 F Cl COOCH2CHCH2 .151 F Cl COOCH2CCH .152 F Cl COOCH2(o-F—C6H5) .153 H Cl COOCH2C6H5 .154 Cl Cl COOCH2C6H5 .155 F Cl COOCH2C6H5 .156 H Br COOCH2C6H5 .157 Cl Br COOCH2C6H5 .158 F Br COOCH2C6H5 .159 Cl CF3 COOCH2C6H5 .160 F CF3 COOCH2C6H5 .161 F CH3 COOCH2C6H5 .162 F OCF3 COOCH2C6H5 .163 F Cl COOCH2CH2Cl .164 H Cl COSCH(CH3)2 .165 Cl Cl COSCH(CH3)2 .166 F Cl COSCH(CH3)2 .167 H Br COSCH(CH3)2 .168 Cl Br COSCH(CH3)2 .169 F Br COSCH(CH3)2 .170 Cl CF3 COSCH(CH3)2 .171 F CF3 COSCH(CH3)2 .172 F CH3 COSCH(CH3)2 .173 F OCF3 COSCH(CH3)2 .174 H Cl CONHCH2CCH .175 Cl Cl CONHCH2CCH .176 F Cl CONHCH2CCH .177 H Br CONHCH2CCH .178 Cl Br CONHCH2CCH .179 F Br CONHCH2CCH .180 Cl CF3 CONHCH2CCH .181 F CF3 CONHCH2CCH .182 F CH3 CONHCH2CCH .183 F OCF3 CONHCH2CCH .184 H Cl CON(CH2CH3)2 .185 Cl Cl CON(CH2CH3)2 .186 F Cl CON(CH2CH3)2 .187 H Br CON(CH2CH3)2 .188 Cl Br CON(CH2CH3)2 .189 F Br CON(CH2CH3)2 .190 Cl CF3 CON(CH2CH3)2 .191 F CF3 CON(CH2CH3)2 .192 F CH3 CON(CH2CH3)2 .193 F OCF3 CON(CH2CH3)2 .194 F Cl CON(CH2CHCH2)2 .195 F Cl CON(CH2CH3)CH2CHCH2 .196 F Cl CONHCH2CH(CH3)2 .197 F Cl CONH(SO2CH3) .198 H Cl CHO .199 Cl Cl CHO .200 F Cl CHO .201 H Br CHO .202 Cl Br CHO .203 F Br CHO .204 Cl CF3 CHO .205 F CF3 CHO .206 F CH3 CHO .207 F OCF3 CHO .208 H Cl CHNOH .209 Cl Cl CHNOH .210 F Cl CHNOH .211 H Br CHNOH .212 Cl Br CHNOH .213 F Br CHNOH .214 Cl CF3 CHNOH .215 F CF3 CHNOH .216 F CH3 CHNOH .217 F OCF3 CHNOH .218 H Cl CHNOCH2CCH .219 Cl Cl CHNOCH2CCH .220 F Cl CHNOCH2CCH .221 H Br CHNOCH2CCH .222 Cl Br CHNOCH2CCH .223 F Br CHNOCH2CCH .224 Cl CF3 CHNOCH2CCH .225 F CF3 CHNOCH2CCH .226 F CH3 CHNOCH2CCH .227 F OCF3 CHNOCH2CCH .228 F Cl CHNOCH3 .229 F Cl CHNOCH2CHCH2 .230 H Cl CH2COOH .231 Cl Cl CH2COOH .232 F Cl CH2COOH .233 H Br CH2COOH .234 Cl Br CH2COOH .235 F Br CH2COOH .236 Cl CF3 CH2COOH .237 F CF3 CH2COOH .238 F CH3 CH2COOH .239 F OCF3 CH2COOH .240 F Cl CH2COOCH3 .241 F Cl CH2COOCH(CH3)2 .242 F Cl CH2COOCH2CHCH2 .243 H Cl CH2CH2COOH .244 Cl Cl CH2CH2COOH .245 F Cl CH2CH2COOH .246 H Br CH2CH2COOH .247 Cl Br CH2CH2COOH .248 F Br CH2CH2COOH .249 Cl CF3 CH2CH2COOH .250 F CF3 CH2CH2COOH .251 F CH3 CH2CH2COOH .252 F OCF3 CH2CH2COOH .253 F Cl CH2CH2COOCH2CH3 .254 F Cl CH2CH2COOCH(CH3)2 .255 F Cl CH2CH2COOCH2CHCH2 .256 F Cl CH2CH2COOCH2C(CH3)CH2 .257 F Cl CH2CH2COOCH2CCH .258 F Cl CH2CH2COOCH(CH3)CCH .259 F Cl CH(OH)CH3 .260 F Cl C(O)CH3 .261 F Cl CN .262 Cl CF3 CN .263 F Cl C(S)NH2 .264 Cl CF3 C(S)NH2
[0416] 91 TABLE 89 A preferred group of compounds of formula I corresponds to the general formula 206 (I89), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I89.
[0417] 92 TABLE 90 Another preferred group of compounds of formula I corresponds to the general formula 207 (I90), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I90.
[0418] 93 TABLE 91 Another preferred group of compounds of formula I corresponds to the general formula 208 (I91), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I91.
[0419] 94 TABLE 92 Another preferred group of compounds of formula I corresponds to the general formula 209 (I92), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I92.
[0420] 95 TABLE 93 Another preferred group of compounds of formula I corresponds to the general formula 210 (I93), in which the sets of correlated substituents R11, R12, and R13 are given in Table C, thus disclosing 627 specific compounds of formula I93.
[0421] 96 TABLE 94 Another preferred group of compounds of formula I corresponds to the general formula 211 (I94), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specifIc compounds of formula I94.
[0422] 97 TABLE 95 Another preferred group of compounds of formula I corresponds to the general formula 212 (I95), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I95.
[0423] 98 TABLE 96 Another preferred group of compounds of formula I corresponds to the general formula 213 (I96), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I96.
[0424] 99 TABLE 97 Another preferred group of compounds of formula I corresponds to the general formula 214 (I97), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I97.
[0425] 100 TABLE 98 Another preferred group of compounds of formula I corresponds to the general formula 215 (I98), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I98.
[0426] 101 TABLE 99 Another preferred group of compounds of formula I corresponds to the general formula 216 (I99), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I99.
[0427] 102 TABLE 100 Another preferred group of compounds of formula I corresponds to the general formula 217 (I100), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I100.
[0428] 103 TABLE 101 Another preferred group of compounds of formula I corresponds to the general formula 218 (I101), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I101.
[0429] 104 TABLE 102 Another preferred group of compounds of formula I corresponds to the general formula 219 (I102), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I102.
[0430] 105 TABLE 103 Another preferred group of compounds of formula I corresPonds to the general formula 220 (I103), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I103.
[0431] 106 TABLE 104 Another preferred group of compounds of formula I corresponds to the general formula 221 (I104), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I104.
[0432] 107 TABLE 105 Another preferred group of compounds of formula I corresponds to the general formula 222 (I105), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula (I105).
[0433] 108 TABLE 106 Another preferred group of compounds of formula I corresponds to the general formula 223 (I106), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I106.
[0434] 109 TABLE 107 Another preferred group of compounds of formula I corresponds to the general formula 224 (I107), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I107.
[0435] 110 TABLE 108 Another preferred group of compounds of formula I corresponds to the general formula 225 (I108), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I108.
[0436] 111 TABLE 109 Another preferred group of compounds of formula I corresponds to the general formula 226 (I109), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I109.
[0437] 112 TABLE 110 Another preferred group of compounds of formula I corresponds to the general formula 227 (I110), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I110.
[0438] 113 TABLE 111 Another preferred group of compounds of formula I corresponds to the general formula 228 (I111), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I111.
[0439] 114 TABLE 112 Another preferred group of compounds of formula I corresponds to the general formula 229 (I112), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I112.
[0440] 115 TABLE 113 Another preferred group of compounds of formula I corresponds to the general formula 230 (I113), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I113.
[0441] 116 TABLE 114 Another preferred group of compounds of formula I corresponds to the general formula 231 (I114), in which the sets of correlated substituents R11, R12 are R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I114.
[0442] 117 TABLE 115 Another preferred group of compounds of formula I corresponds to the general formula 232 (I115), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I115.
[0443] 118 TABLE 116 Another preferred group of compounds of formula I corresponds to the general formula 233 (I116), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific compounds of formula I116.
[0444] 119 TABLE 117 Another preferred group of compounds of formula I corresponds to the general formula 234 (I117), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I117.
[0445] 120 TABLE 118 Another preferred group of compounds of formula I corresponds to the general formula 235 (I118), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I118.
[0446] 121 TABLE 119 Another preferred group of compounds of formula I corresponds to the general formula 236 (I119), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I119.
[0447] 122 TABLE 120 Another preferred group of compounds of formula I corresponds to the general formula 237 (I120), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I120.
[0448] 123 TABLE 121 Another preferred group of compounds of formula I corresponds to the general formula 238 (I121), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I121.
[0449] 124 TABLE 122 Another preferred group of compounds of formula I corresponds to the general formula 239 (I122), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I122.
[0450] 125 TABLE 123 Another preferred group of compounds of formula I corresponds to the general formula 240 (I123), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I123.
[0451] 126 TABLE 124 Another preferred group of compounds of formula I corresponds to the general formula 241 (I124), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I124.
[0452] 127 TABLE 125 Another preferred group of compounds of formula I corresponds to the general formula 242 (I125), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I125.
[0453] 128 TABLE 126 Another preferred group of compounds of formula I corresponds to the general formula 243 (I126), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I126.
[0454] 129 TABLE 127 Another preferred group of compounds of formula I corresponds to the general formula 244 (I127), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I127.
[0455] 130 TABLE 128 Another preferred group of compounds of formula I corresponds to the general formula 245 (I128), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I128.
[0456] 131 TABLE 129 Another preferred group of compounds of formula I corresponds to the general formula 246 (I129), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I129.
[0457] 132 TABLE 130 Another preferred group of compounds of formula I corresponds to the general formula 247 (I130), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I130.
[0458] 133 TABLE 131 Another preferred group of compounds of formula I corresponds to the general formula 248 (I131), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I131.
[0459] 134 TABLE 132 Another preferred group of compounds of formula I corresponds to the general formula 249 (I132), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I132.
[0460] 135 TABLE 133 Another preferred group of compounds of formula I corresponds to the general formula 250 (I133), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I133.
[0461] 136 TABLE 134 Another preferred group of compounds of formula I corresponds to the general formula 251 (I134), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I134.
[0462] 137 TABLE 135 Another preferred group of compounds of formula I corresponds to the general formula 252 (I135), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I135.
[0463] 138 TABLE 136 Another preferred group of compounds of formula I corresponds to the general formula 253 (I136), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I136.
[0464] 139 TABLE 137 Another preferred group of compounds of formula I corresponds to the general formula 254 (I137), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I137.
[0465] 140 TABLE 138 Another preferred group of compounds of formula I corresponds to the general formula 255 (I138), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I138.
[0466] 141 TABLE 139 Another preferred group of compounds of formula I corresponds to the general formula 256 (I139), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I139.
[0467] 142 TABLE 140 Another preferred group of compounds of formula I corresponds to the general formula 257 (I140), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I140.
[0468] 143 TABLE 141 Another preferred group of compounds of formula I corresponds to the general formula 258 (I141), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I141.
[0469] 144 TABLE 142 Another preferred group of compounds of formula I corresponds to the general formula 259 (I142), in which the sets of correlated substituents R11, R12 and R13 are given in Table C, thus disclosing 627 specific com- pounds of formula I142.
[0470] 145 TABLE C Compd. No. R11 R12 R13 .001 H Cl CH2CHCH2 .002 Cl Cl CH2CHCH2 .003 F Cl CH2CHCH2 .004 H Br CH2CHCH2 .005 Cl Br CH2CHCH2 .006 F Br CH2CHCH2 .007 H I CH2CHCH2 .008 Cl I CH2CHCH2 .009 F I CH2CHCH2 .010 H CH3 CH2CHCH2 .011 Cl CH3 CH2CHCH2 .012 F CH3 CH2CHCH2 .013 H OH CH2CHCH2 .014 Cl OH CH2CHCH2 .015 F OH CH2CHCH2 .016 H OCF3 CH2CHCH2 .017 Cl OCF3 CH2CHCH2 .018 F OCF3 CH2CHCH2 .019 H CHO CH2CHCH2 .020 Cl CHO CH2CHCH2 .021 F CHO CH2CHCH2 .022 H CHF2 CH2CHCH2 .023 Cl CHF2 CH2CHCH2 .024 F CHF2 CH2CHCH2 .025 H COOH CH2CHCH2 .026 Cl COOH CH2CHCH2 .027 F COOH CH2CHCH2 .028 H COOCH2CH3 CH2CHCH2 .029 CL COOCH2CH3 CH2CHCH2 .030 F COOCH2CH3 CH2CHCH2 .031 H CN CH2CHCH2 .032 Cl CN CH2CHCH2 .033 F CN CH2CHCH2 .034 H Cl CH2C6H5 .035 Cl Cl CH2C6H5 .036 F Cl CH2C6H5 .037 H Br CH2C6H5 .038 Cl Br CH2C6H5 .039 F Br CH2C6H5 .040 H I CH2C6H5 .041 Cl I CH2C6H5 .042 F I CH2C6H5 .043 H CH3 CH2C6H5 .044 Cl CH3 CH2C6H5 .045 F CH3 CH2C6H5 .046 H OH CH2C6H5 .047 Cl OH CH2C6H5 .048 F OH CH2C6H5 .049 H OCF3 CH2C6H5 .050 Cl OCF3 CH2C6H5 .051 F OCF3 CH2C6H5 .052 H CHO CH2C6H5 .053 Cl CHO CH2C6H5 .054 F CHO CH2C6H5 .055 H CHF2 CH2C6H5 .056 Cl CHF2 CH2C6H5 .057 F CHF2 CH2C6H5 .058 H COOH CH2C6H5 .059 Cl COOH CH2C6H5 .060 F COOH CH2C6H5 .061 H COOCH2CH3 CH2C6H5 .062 Cl COOCH2CH3 CH2C6H5 .063 F COOCH2CH3 CH2C6H5 .064 H CN CH2C6H5 .065 Cl CN CH2C6H5 .066 F CN CH2C6H5 .067 H Cl CH2CCH .068 Cl Cl CH2CCH .069 F Cl CH2CCH .070 H Br CH2CCH .071 Cl Br CH2CCH .072 F Br CH2CCH .073 H I CH2CCH .074 Cl I CH2CCH .075 F I CH2CCH .076 H CH3 CH2CCH .077 Cl CH3 CH2CCH .078 F CH3 CH2CCH .079 H OH CH2CCH .080 Cl OH CH2CCH .081 F OH CH2CCH .082 H OCF3 CH2CCH .083 Cl OCF3 CH2CCH .084 F OCF3 CH2CCH .085 H CHO CH2CCH .086 Cl CHO CH2CCH .087 F CHO CH2CCH .088 H CHF2 CH2CCH .089 Cl CHF2 CH2CCH .090 F CHF2 CH2CCH .091 H COOH CH2CCH .092 Cl COOH CH2CCH .093 F COOH CH2CCH .094 H COOCH2CH3 CH2CCH .095 Cl COOCH2CH3 CH2CCH .096 F COOCH2CH3 CH2CCH .097 H CN CH2CCH .098 Cl CN CH2CCH .099 F CN CH2CCH .100 H Cl CH2COOH .101 Cl Cl CH2COOH .102 F Cl CH2COOH .103 H Br CH2COOH .104 Cl Br CH2COOH .105 F Br CH2COOH .106 H I CH2COOH .107 Cl I CH2COOH .108 F I CH2COOH .109 H CH3 CH2COOH .110 Cl CH3 CH2COOH .111 F CH3 CH2COOH .112 H OH CH2COOH .113 Cl OH CH2COOH .114 F OH CH2COOH .115 H OCF3 CH2COOH .116 Cl OCF3 CH2COOH .117 F OCF3 CH2COOH .118 H CHO CH2COOH .119 Cl CHO CH2COOH .120 F CHO CH2COOH .121 H CHF2 CH2COOH .122 Cl CHF2 CH2COOH .123 F CHF2 CH2COOH .124 H COOH CH2COOH .125 Cl COOH CH2COOH .126 F COOH CH2COOH .127 H COOCH2CH3 CH2COOH .128 Cl COOCH2CH3 CH2COOH .129 F COOCH2CH3 CH2COOH .130 H CN CH2COOH .131 Cl CN CH2COOH .132 F CN CH2COOH .133 H Cl CH2COOCH3 .134 Cl Cl CH2COOCH3 .135 F Cl CH2COOCH3 .136 H Br CH2COOCH3 .137 Cl Br CH2COOCH3 .138 F Br CH2COOCH3 .139 H I CH2COOCH3 .140 Cl I CH2COOCH3 .141 F I CH2COOCH3 .142 H CH3 CH2COOCH3 .143 Cl CH3 CH2COOCH3 .144 F CH3 CH2COOCH3 .145 H OH CH2COOCH3 .146 Cl OH CH2COOCH3 .147 F OH CH2COOCH3 .148 H OCF3 CH2COOCH3 .149 Cl OCF3 CH2COOCH3 .150 F OCF3 CH2COOCH3 .151 H CHO CH2COOCH3 .152 Cl CHO CH2COOCH3 .153 F CHO CH2COOCH3 .154 H CHF2 CH2COOCH3 .155 Cl CHF2 CH2COOCH3 .156 F CHF2 CH2COOCH3 .157 H COOH CH2COOCH3 .158 Cl COOH CH2COOCH3 .159 F COOH CH2COOCH3 .160 H COOCH2CH3 CH2COOCH3 .161 Cl COOCH2CH3 CH2COOCH3 .162 F COOCH2CH3 CH2COOCH3 .163 H CN CH2COOCH3 .164 Cl CN CH2COOCH3 .165 F CN CH2COOCH3 .166 H Cl OH .167 Cl Cl OH .168 F Cl OH .169 H Br OH .170 Cl Br OH .171 F Br OH .172 H I OH .173 Cl I OH .174 F I OH .175 H CH3 OH .176 Cl CH3 OH .177 F CH3 OH .178 H OH OH .179 Cl OH OH .180 F OH OH .181 H OCF3 OH .182 Cl OCF3 OH .183 F OCF3 OH .184 H CHO OH .185 Cl CHO OH .186 F CHO OH .187 H CHF2 OH .188 Cl CHF2 OH .189 F CHF2 OH .190 H COOH OH .191 Cl COOH OH .192 F COOH OH .193 H COOCH2CH3 OH .194 Cl COOCH2CH3 OH .195 F COOCH2CH3 OH .196 H CN OH .197 Cl CN OH .198 F CN OH .199 H Cl OCH2CHCH2 .200 Cl Cl OCH2CHCH2 .201 F Cl OCH2CHCH2 .202 H Br OCH2CHCH2 .203 Cl Br OCH2CHCH2 .204 F Br OCH2CHCH2 .205 H I OCH2CHCH2 .206 Cl I OCH2CHCH2 .207 F I OCH2CHCH2 .208 H CH3 OCH2CHCH2 .209 Cl CH3 OCH2CHCH2 .210 F CH3 OCH2CHCH2 .211 H OH OCH2CHCH2 .212 Cl OH OCH2CHCH2 .213 F OH OCH2CHCH2 .214 H OCF3 OCH2CHCH2 .215 Cl OCF3 OCH2CHCH2 .216 F OCF3 OCH2CHCH2 .217 H CHO OCH2CHCH2 .218 Cl CHO OCH2CHCH2 .219 F CHO OCH2CHCH2 .220 H CHF2 OCH2CHCH2 .221 Cl CHF2 OCH2CHCH2 .222 F CHF2 OCH2CHCH2 .223 H COOH OCH2CHCH2 .224 Cl COOH OCH2CHCH2 .225 F COOH OCH2CHCH2 .226 H COOCH2CH3 OCH2CHCH2 .227 Cl COOCH2CH3 OCH2CHCH2 .228 F COOCH2CH3 OCH2CHCH2 .229 H CN OCH2CHCH2 .230 Cl CN OCH2CHCH2 .231 F CN OCH2CHCH2 .232 H Cl OCH2C6H5 .233 Cl Cl OCH2C6H5 .234 F Cl OCH2C6H5 .235 H Br OCH2C6H5 .236 Cl Br OCH2C6H5 .237 F Br OCH2C6H5 .238 H I OCH2C6H5 .239 Cl I OCH2C6H5 .240 F I OCH2C6H5 .241 H CH3 OCH2C6H5 .242 Cl CH3 OCH2C6H5 .243 F CH3 OCH2C6H5 .244 H OH OCH2C6H5 .245 Cl OH OCH2C6H5 .246 F OH OCH2C6H5 .247 H OCF3 OCH2C6H5 .248 Cl OCF3 OCH2C6H5 .249 F OCF3 OCH2C6H5 .250 H CHO OCH2C6H5 .251 Cl CHO OCH2C6H5 .252 F CHO OCH2C6H5 .253 H CHF2 OCH2C6H5 .254 Cl CHF2 OCH2C6H5 .255 F CHF2 OCH2C6H5 .256 H COOH OCH2C6H5 .257 Cl COOH OCH2C6H5 .258 F COOH OCH2C6H5 .259 H COOCH2CH3 OCH2C6H5 .260 Cl COOCH2CH3 OCH2C6H5 .261 F COOCH2CH3 OCH2C6H5 .262 H CN OCH2C6H5 .263 Cl CN OCH2C6H5 .264 F CN OCH2C6H5 .265 H Cl OCH2COOH .266 Cl Cl OCH2COOH .267 F Cl OCH2COOH .268 H Br OCH2COOH .269 Cl Br OCH2COOH .270 F Br OCH2COOH .271 H I OCH2COOH .272 Cl I OCH2COOH .273 F I OCH2COOH .274 H CH3 OCH2COOH .275 Cl CH3 OCH2COOH .276 F CH3 OCH2COOH .277 H OH OCH2COOH .278 Cl OH OCH2COOH .279 F OH OCH2COOH .280 H OCF3 OCH2COOH .281 Cl OCF3 OCH2COOH .282 F OCF3 OCH2COOH .283 H CHO OCH2COOH .284 Cl CHO OCH2COOH .285 F CHO OCH2COOH .286 H CHF2 OCH2COOH .287 Cl CHF2 OCH2COOH .288 F CHF2 OCH2COOH .289 H COOH OCH2COOH .290 Cl COOH OCH2COOH .291 F COOH OCH2COOH .292 H COOCH2CH3 OCH2COOH .293 Cl COOCH2CH3 OCH2COOH .294 F COOCH2CH3 OCH2COOH .295 H CN OCH2COOH .296 Cl CN OCH2COOH .297 F CN OCH2COOH .298 H Cl OCH2COOCH3 .299 Cl Cl OCH2COOCH3 .300 F Cl OCH2COOCH3 .301 H Br OCH2COOCH3 .302 Cl Br OCH2COOCH3 .303 F Br OCH2COOCH3 .304 H I OCH2COOCH3 .305 Cl I OCH2COOCH3 .306 F I OCH2COOCH3 .307 H CH3 OCH2COOCH3 .308 Cl CH3 OCH2COOCH3 .309 F CH3 OCH2COOCH3 .310 H OH OCH2COOCH3 .311 Cl OH OCH2COOCH3 .312 F OH OCH2COOCH3 .313 H OCF3 OCH2COOCH3 .314 Cl OCF3 OCH2COOCH3 .315 F OCF3 OCH2COOCH3 .316 H CHO OCH2COOCH3 .317 Cl CHO OCH2COOCH3 .318 F CHO OCH2COOCH3 .319 H CHF2 OCH2COOCH3 .320 Cl CHF2 OCH2COOCH3 .321 F CHF2 OCH2COOCH3 .322 H COOH OCH2COOCH3 .323 Cl COOH OCH2COOCH3 .324 F COOH OCH2COOCH3 .325 H COOCH2CH3 OCH2COOCH3 .326 Cl COOCH2CH3 OCH2COOCH3 .327 F COOCH2CH3 OCH2COOCH3 .328 H CN OCH2COOCH3 .329 Cl CN OCH2COOCH3 .330 F CN OCH2COOCH3 .331 H Cl CH2CHO .332 Cl Cl CH2CHO .333 F Cl CH2CHO .334 H Br CH2CHO .335 Cl Br CH2CHO .336 F Br CH2CHO .337 H I CH2CHO .338 Cl I CH2CHO .339 F I CH2CHO .340 H CH3 CH2CHO .341 Cl CH3 CH2CHO .342 F CH3 CH2CHO .343 H OH CH2CHO .344 Cl OH CH2CHO .345 F OH CH2CHO .346 H OCF3 CH2CHO .347 Cl OCF3 CH2CHO .348 F OCF3 CH2CHO .349 H CHO CH2CHO .350 Cl CHO CH2CHO .351 F CHO CH2CHO .352 H CHF2 CH2CHO .353 Cl CHF2 CH2CHO .354 F CHF2 CH2CHO .355 H COOH CH2CHO .356 Cl COOH CH2CHO .357 F COOH CH2CHO .358 H COOCH2CH3 CH2CHO .359 Cl COOCH2CH3 CH2CHO .360 F COOCH2CH3 CH2CHO .361 H CN CH2CHO .362 Cl CN CH2CHO .363 F CN CH2CHO .364 H Cl OCH2CHO .365 Cl Cl OCH2CHO .366 F Cl OCH2CHO .367 H Br OCH2CHO .368 Cl Br OCH2CHO .369 F Br OCH2CHO .370 H I OCH2CHO .371 Cl I OCH2CHO .372 F I OCH2CHO .373 H CH3 OCH2CHO .374 Cl CH3 OCH2CHO .375 F CH3 OCH2CHO .376 H OH OCH2CHO .377 Cl OH OCH2CHO .378 F OH OCH2CHO .379 H OCF3 OCH2CHO .380 Cl OCF3 OCH2CHO .381 F OCF3 OCH2CHO .382 H CHO OCH2CHO .383 Cl CHO OCH2CHO .384 F CHO OCH2CHO .385 H CHF2 OCH2CHO .386 Cl CHF2 OCH2CHO .387 F CHF2 OCH2CHO .388 H COOH OCH2CHO .389 Cl COOH OCH2CHO .390 F COOH OCH2CHO .391 H COOCH2CH3 OCH2CHO .392 Cl COOCH2CH3 OCH2CHO .393 F COOCH2CH3 OCH2CHO .394 H CN OCH2CHO .395 Cl CN OCH2CHO .396 F CN OCH2CHO .397 H Cl OCH3 .398 Cl Cl OCH3 .399 F Cl OCH3 .400 H Br OCH3 .401 Cl Br OCH3 .402 F Br OCH3 .403 H I OCH3 .404 Cl I OCH3 .405 F I OCH3 .406 H CH3 OCH3 .407 Cl CH3 OCH3 .408 F CH3 OCH3 .409 H OH OCH3 .410 Cl OH OCH3 .411 F OH OCH3 .412 H OCF3 OCH3 .413 Cl OCF3 OCH3 .414 F OCF3 OCH3 .415 H CHO OCH3 .416 Cl CHO OCH3 .417 F CHO OCH3 .418 H CHF2 OCH3 .419 Cl CHF2 OCH3 .420 F CHF2 OCH3 .421 H COOH OCH3 .422 Cl COOH OCH3 .423 F COOH OCH3 .424 H COOCH2CH3 OCH3 .425 Cl COOCH2CH3 OCH3 .426 F COOCH2CH3 OCH3 .427 H CN OCH3 .428 Cl CN OCH3 .429 F CN OCH3 .430 H Cl CH2OCH3 .431 Cl Cl CH2OCH3 .432 F Cl CH2OCH3 .433 H Br CH2OCH3 .434 Cl Br CH2OCH3 .435 F Br CH2OCH3 .436 H I CH2OCH3 .437 Cl I CH2OCH3 .438 F I CH2OCH3 .439 H CH3 CH2OCH3 .440 Cl CH3 CH2OCH3 .441 F CH3 CH2OCH3 .442 H OH CH2OCH3 .443 Cl OH CH2OCH3 .444 F OH CH2OCH3 .445 H OCF3 CH2OCH3 .446 Cl OCF3 CH2OCH3 .447 F OCF3 CH2OCH3 .448 H CHO CH2OCH3 .449 Cl CHO CH2OCH3 .450 F CHO CH2OCH3 .451 H CHF2 CH2OCH3 .452 Cl CHF2 CH2OCH3 .453 F CHF2 CH2OCH3 .454 H COOH CH2OCH3 .455 Cl COOH CH2OCH3 .456 F COOH CH2OCH3 .457 H COOCH2CH3 CH2OCH3 .458 Cl COOCH2CH3 CH2OCH3 .459 F COOCH2CH3 CH2OCH3 .460 H CN CH2OCH3 .461 Cl CN CH2OCH3 .462 F CN CH2OCH3 .463 H Cl CH2SCH3 .464 Cl Cl CH2SCH3 .465 F Cl CH2SCH3 .466 H Br CH2SCH3 .467 Cl Br CH2SCH3 .468 F Br CH2SCH3 .469 H I CH2SCH3 .470 Cl I CH2SCH3 .471 F I CH2SCH3 .472 H CH3 CH2SCH3 .473 Cl CH3 CH2SCH3 .474 F CH3 CH2SCH3 .475 H OH CH2SCH3 .476 Cl OH CH2SCH3 .477 F OH CH2SCH3 .478 H OCF3 CH2SCH3 .479 Cl OCF3 CH2SCH3 .480 F OCF3 CH2SCH3 .481 H CHO CH2SCH3 .482 Cl CHO CH2SCH3 .483 F CHO CH2SCH3 .484 H CHF2 CH2SCH3 .485 Cl CHF2 CH2SCH3 .486 F CHF2 CH2SCH3 .487 H COOH CH2SCH3 .488 Cl COOH CH2SCH3 .489 F COOH CH2SCH3 .490 H COOCH2CH3 CH2SCH3 .491 Cl COOCH2CH3 CH2SCH3 .492 F COOCH2CH3 CH2SCH3 .493 H CN CH2SCH3 .494 Cl CN CH2SCH3 .495 F CN CH2SCH3 .496 H Cl OCH2OCH3 .497 Cl Cl OCH2OCH3 .498 F Cl OCH2OCH3 .499 H Br OCH2OCH3 .500 Cl Br OCH2OCH3 .501 F Br OCH2OCH3 .502 H I OCH2OCH3 .503 Cl I OCH2OCH3 .504 F I OCH2OCH3 .505 H CH3 OCH2OCH3 .506 Cl CH3 OCH2OCH3 .507 F CH3 OCH2OCH3 .508 H OH OCH2OCH3 .509 Cl OH OCH2OCH3 .510 F OH OCH2OCH3 .511 H OCF3 OCH2OCH3 .512 Cl OCF3 OCH2OCH3 .513 F OCF3 OCH2OCH3 .514 H CHO OCH2OCH3 .515 Cl CHO OCH2OCH3 .516 F CHO OCH2OCH3 .517 H CHF2 OCH2OCH3 .518 Cl CHF2 OCH2OCH3 .519 F CHF2 OCH2OCH3 .520 H COOH OCH2OCH3 .521 Cl COOH OCH2OCH3 .522 F COOH OCH2OCH3 .523 H COOCH2CH3 OCH2OCH3 .524 Cl COOCH2CH3 OCH2OCH3 .525 F COOCH2CH3 OCH2OCH3 .526 H CN OCH2OCH3 .527 Cl CN OCH2OCH3 .528 F CN OCH2OCH3 .529 H Cl OCH2SCH3 .530 Cl Cl OCH2SCH3 .531 F Cl OCH2SCH3 .532 H Br OCH2SCH3 .533 Cl Br OCH2SCH3 .534 F Br OCH2SCH3 .535 H I OCH2SCH3 .536 Cl I OCH2SCH3 .537 F I OCH2SCH3 .538 H CH3 OCH2SCH3 .539 Cl CH3 OCH2SCH3 .540 F CH3 OCH2SCH3 .541 H OH OCH2SCH3 .542 Cl OH OCH2SCH3 .543 F OH OCH2SCH3 .544 H OCF3 OCH2SCH3 .545 Cl OCF3 OCH2SCH3 .546 F OCF3 OCH2SCH3 .547 H CHO OCH2SCH3 .548 Cl CHO OCH2SCH3 .549 F CHO OCH2SCH3 .550 H CHF2 OCH2SCH3 .551 Cl CHF2 OCH2SCH3 .552 F CHF2 OCH2SCH3 .553 H COOH OCH2SCH3 .554 Cl COOH OCH2SCH3 .555 F COOH OCH2SCH3 .556 H COOCH2CH3 OCH2SCH3 .557 Cl COOCH2CH3 OCH2SCH3 .558 F COOCH2CH3 OCH2SCH3 .559 H CN OCH2SCH3 .560 Cl CN OCH2SCH3 .561 F CN OCH2SCH3 .562 H Cl OCH2CH2CN .563 Cl Cl OCH2CH2CN .564 F Cl OCH2CH2CN .565 H Br OCH2CH2CN .566 Cl Br OCH2CH2CN .567 F Br OCH2CH2CN .568 H I OCH2CH2CN .569 Cl I OCH2CH2CN .570 F I OCH2CH2CN .571 H CH3 OCH2CH2CN .572 Cl CH3 OCH2CH2CN .573 F CH3 OCH2CH2CN .574 H OH OCH2CH2CN .575 Cl OH OCH2CH2CN .576 F OH OCH2CH2CN .577 H OCF3 OCH2CH2CN .578 Cl OCF3 OCH2CH2CN .579 F OCF3 OCH2CH2CN .580 H CHO OCH2CH2CN .581 Cl CHO OCH2CH2CN .582 F CHO OCH2CH2CN .583 H CHF2 OCH2CH2CN .584 Cl CHF2 OCH2CH2CN .585 F CHF2 OCH2CH2CN .586 H COOH OCH2CH2CN .587 Cl COOH OCH2CH2CN .588 F COOH OCH2CH2CN .589 H COOCH2CH3 OCH2CH2CN .590 Cl COOCH2CH3 OCH2CH2CN .591 F COOCH2CH3 OCH2CH2CN .592 H CN OCH2CH2CN .593 Cl CN OCH2CH2CN .594 F CN OCH2CH2CN .595 H Cl CH2CH2CN .596 Cl Cl CH2CH2CN .597 F Cl CH2CH2CN .598 H Br CH2CH2CN .599 Cl Br CH2CH2CN .600 F Br CH2CH2CN .601 H I CH2CH2CN .602 Cl I CH2CH2CN .603 F I CH2CH2CN .604 H CH3 CH2CH2CN .605 Cl CH3 CH2CH2CN .606 F CH3 CH2CH2CN .607 H OH CH2CH2CN .608 Cl OH CH2CH2CN .609 F OH CH2CH2CN .610 H OCF3 CH2CH2CN .611 Cl OCF3 CH2CH2CN .612 F OCF3 CH2CH2CN .613 H CHO CH2CH2CN .614 Cl CHO CH2CH2CN .615 F CHO CH2CH2CN .616 H CHF2 CH2CH2CN .617 Cl CHF2 CH2CH2CN .618 F CHF2 CH2CH2CN .619 H COOH CH2CH2CN .620 Cl COOH CH2CH2CN .621 F COOH CH2CH2CN .622 H COOCH2CH3 CH2CH2CN .623 Cl COOCH2CH3 CH2CH2CN .624 F COOCH2CH3 CH2CH2CN .625 H CN CH2CH2CN .626 Cl CN CH2CH2CN .627 F CN CH2CH2CN
[0471] 146 TABLE 143 A preferred group of compounds of formula I corresponds to the general formula 260 (I143), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I143.
[0472] 147 TABLE 144 Another preferred group of compounds of formula I corresponds to the general formula 261 (I144), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I444.
[0473] 148 TABLE 145 Another preferred group of compounds of formula I corresponds to the general formula 262 (I145), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific com- pounds of formula I145.
[0474] 149 TABLE 146 Another preferred group of compounds of formula I corresponds to the general formula 263 (I146), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I146.
[0475] 150 TABLE 147 Another preferred group of compounds of formula I corresponds to the general formula 264 (I147), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific com- pounds of formula I147.
[0476] 151 TABLE 148 Another preferred group of compounds of formula I corresponds to the general formula 265 (I148), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific com- pounds of formula I148.
[0477] 152 TABLE 149 Another preferred group of compounds of formula I corresponds to the general formula 266 (I149), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific com- pounds of formula I149.
[0478] 153 TABLE 150 Another preferred group of compounds of formula I corresponds to the general formula 267 (I150), in which the sets of correlaqted substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I150.
[0479] 154 TABLE 151 Another preferred group of compounds of formula I corresponds to the general formula 268 (I151), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I151.
[0480] 155 TABLE 152 Another preferred group of compounds of formula I corresponds to the general formula 269 (I152), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I152.
[0481] 156 TABLE 153 Another preferred group of compounds of formula I corresponds to the general formula 270 (I153), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I153.
[0482] 157 TABLE 154 Another preferred group of compounds of formula I corresponds to the general formula 271 (I154), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I154.
[0483] 158 TABLE 155 Another preferred group of compounds of formula I corresponds to the general formula 272 (I155), in which the sets of correlated substituents R11 , R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I155.
[0484] 159 TABLE 156 Another preferred froup of compounds of formula I corresponds to the general formula 273 (I156), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I156.
[0485] 160 TABLE 157 Another preferred group of compounds of formula I corresponds to the general formula 274 (I157), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I157.
[0486] 161 TABLE 158 Another preferred group of compounds of formula I corresponds to the general formula 275 R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I158.
[0487] 162 TABLE 159 Another preferred group of compounds of formula I corresponds to the general formula 276 (I159, in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I159.
[0488] 163 TABLE 160 Another preferred group of compounds of formula I corresponds to the general formula 277 (I160), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I160.
[0489] 164 TABLE 161 Another preferred group of compounds of formula I corresponds to the general formula 278 (I161), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I161.
[0490] 165 TABLE 162 Another preferred group of compounds of formula I corresponds to the general formula 279 (I162), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I162.
[0491] 166 TABLE 163 Another preferred group of compounds of formula I corresponds to the general formula 280 (I163), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I163.
[0492] 167 TABLE 164 Another preferred group of compounds of formula I corresponds to the general formula 281 (I164), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I164.
[0493] 168 TABLE 165 Another preferred group of compounds of formula I corresponds to the general formula 282 (I165), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I165.
[0494] 169 TABLE 166 Another preferred group of compounds of formula I corresponds to the general formula 283 (I166), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I166.
[0495] 170 TABLE 167 Another preferred group of compounds of formula I corresponds to the general formula 284 (I167), in which the sets of correlated cubstituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I167.
[0496] 171 TABLE 168 Another preferred group of compounds of formula I corresponds to the general formula 285 (I168), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I168.
[0497] 172 TABLE 169 Another preferred group of compounds of formula I corresponds to the general formula 286 (I169), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I169.
[0498] 173 TABLE 170 Another preferred group of compounds of formula I corresponds to the general formula 287 (I170), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I170.
[0499] 174 TABLE 171 Another preffered group of compounds of formula I corresponds to the general formula 288 (I171), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I171.
[0500] 175 TABLE 172 Another preferred froup of compounds of formula I corresponds to the general formula 289 (I172), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I172.
[0501] 176 TABLE 173 Another preferred group of compounds of formula I corresponds to the general formula 290 (I173), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I173.
[0502] 177 TABLE 174 Another preferred group of compounds of formula I corresponds to the general formula 291 (I174), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I174.
[0503] 178 TABLE 175 Another preferred group of compounds of formula I corresponds to the general formula 292 (I175), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I175.
[0504] 179 TABLE 176 Another preferred group of compounds of formula I corresponds to the general formula 293 (I176), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I176.
[0505] 180 TABLE 177 Another preferred group of compounds of formula I corresponds to the general formula 294 (I177), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I177.
[0506] 181 TABLE 178 Another preferred group of compounds of formula I corresponds to the general formula 295 (I178), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I178.
[0507] 182 TABLE 179 Another preferred group of compounds of formula I corresponds to the general formula 296 (I179), in whichy the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I179.
[0508] 183 TABLE 180 Another preferred group of compounds of formula I corresponds to the general formula 297 (I180), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I180.
[0509] 184 TABLE 181 Another preferred group of compounds of formula I corresponds to the general formula 298 (I181), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I181.
[0510] 185 TABLE 182 Another preferred group of compounds of formula I corresponds to the general formula 299 (I182), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I182.
[0511] 186 TABLE 183 Another preferred group of compounds of formula I corresponds to the general formula 300 (I183), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I183.
[0512] 187 TABLE 184 Another preferred group of compounds of formula I corresponds to the general formula 301 (I184), in which the sets of compounds substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I184.
[0513] 188 TABLE 185 Another preferred group of compounds of formula I corresponds to the general formula 302 (I185), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I185.
[0514] 189 TABLE 186 Another preferred group of compounds of formula I corresponds to the general formula 303 (I186), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I186.
[0515] 190 TABLE 187 Another preferred group of compounds of formula I corresponds to the general formula 304 (I187), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I187.
[0516] 191 TABLE 188 Another preferred group of compounds of formula I corresponds to the general formula 305 (I186), in which the sets of correlatred substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I188.
[0517] 192 TABLE 189 Another pre ferred group of compounds of formula I corresponds to the general formula 306 (I189), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I189.
[0518] 193 TABLE 190 Another preferred group of compounds of formula I corresponds to the general formula 307 (I190), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I190.
[0519] 194 TABLE 191 Another preferred group of compounds of formula I corresponds to the general formula 308 (I191), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I191.
[0520] 195 TABLE 192 Another preferred group of compounds of formula I corresponds to the general formula 309 (I192), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I192.
[0521] 196 TABLE 193 Another preferred group of compounds of formula I corresponds to the general formula 310 (I193), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I193.
[0522] 197 TABLE 194 Another preferred group of compounds of formula I corresponds to the general formula 311 (I194), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I194.
[0523] 198 TABLE 195 Another preferred group of compounds of formula I corresponds to the general formula 312 (I195), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I195.
[0524] 199 TABLE 196 Another preferred group of compounds of formula I corresponds to the general formula 313 (I196), in which the sets of correlated substituents R11, R12 and R13 are given in Table D, thus disclosing 627 specific compounds of formula I196.
[0525] 200 TABLE D Compd. No. R11 R12 R13 .001 H Cl CH2CHCH2 .002 Cl Cl CH2CHCH2 .003 F Cl CH2CHCH2 .004 H Br CH2CHCH2 .005 Cl Br CH2CHCH2 .006 F Br CH2CHCH2 .007 H I CH2CHCH2 .008 Cl I CH2CHCH2 .009 F I CH2CHCH2 .010 H CH3 CH2CHCH2 .011 Cl CH3 CH2CHCH2 .012 F CH3 CH2CHCH2 .013 H OH CH2CHCH2 .014 Cl OH CH2CHCH2 .015 F OH CH2CHCH2 .016 H OCF3 CH2CHCH2 .017 Cl OCF3 CH2CHCH2 .018 F OCF3 CH2CHCH2 .019 H CHO CH2CHCH2 .020 Cl CHO CH2CHCH2 .021 F CHO CH2CHCH2 .022 H CHF2 CH2CHCH2 .023 Cl CHF2 CH2CHCH2 .024 F CHF2 CH2CHCH2 .025 H COOH CH2CHCH2 .026 Cl COOH CH2CHCH2 .027 F COOH CH2CHCH2 .028 H COOCH2CH3 CH2CHCH2 .029 Cl COOCH2CH3 CH2CHCH2 .030 F COOCH2CH3 CH2CHCH2 .031 H CN CH2CHCH2 .032 Cl CN CH2CHCH2 .033 F CN CH2CHCH2 .034 H Cl CH2C6H5 .035 Cl Cl CH2C6H5 .036 F Cl CH2C6H5 .037 H Br CH2C6H5 .038 Cl Br CH2C6H5 .039 F Br CH2C6H5 .040 H I CH2C6H5 .041 Cl I CH2C6H5 .042 F I CH2C6H5 .043 H CH3 CH2C6H5 .044 Cl CH3 CH2C6H5 .045 F CH3 CH2C6H5 .046 H OH CH2C6H5 .047 Cl OH CH2C6H5 .048 F OH CH2C6H5 .049 H OCF3 CH2C6H5 .050 Cl OCF3 CH2C6H5 .051 F OCF3 CH2C6H5 .052 H CHO CH2C6H5 .053 Cl CHO CH2C6H5 .054 F CHO CH2C6H5 .055 H CHF2 CH2C6H5 .056 Cl CHF2 CH2C6H5 .057 F CHF2 CH2C6H5 .058 H COOH CH2C6H5 .059 Cl COOH CH2C6H5 .060 F COOH CH2C6H5 .061 H COOCH2CH3 CH2C6H5 .062 Cl COOCH2CH3 CH2C6H5 .063 F COOCH2CH3 CH2C6H5 .064 H CN CH2C6H5 .065 Cl CN CH2C6H5 .066 F CN CH2C6H5 .067 H Cl CH2CCH .068 Cl Cl CH2CCH .069 F Cl CH2CCH .070 H Br CH2CCH .071 Cl Br CH2CCH .072 F Br CH2CCH .073 H I CH2CCH .074 Cl I CH2CCH .075 F I CH2CCH .076 H CH3 CH2CCH .077 Cl CH3 CH2CCH .078 F CH3 CH2CCH .079 H OH CH2CCH .080 Cl OH CH2CCH .081 F OH CH2CCH .082 H OCF3 CH2CCH .083 Cl OCF3 CH2CCH .084 F OCF3 CH2CCH .085 H CHO CH2CCH .086 Cl CHO CH2CCH .087 F CHO CH2CCH .088 H CHF2 CH2CCH .089 Cl CHF2 CH2CCH .090 F CHF2 CH2CCH .091 H COOH CH2CCH .092 Cl COOH CH2CCH .093 F COOH CH2CCH .094 H COOCH2CH3 CH2CCH .095 Cl COOCH2CH3 CH2CCH .096 F COOCH2CH3 CH2CCH .097 H CN CH2CCH .098 Cl CN CH2CCH .099 F CN CH2CCH .100 H Cl CH2COOH .101 Cl Cl CH2COOH .102 F Cl CH2COOH .103 H Br CH2COOH .104 Cl Br CH2COOH .105 F Br CH2COOH .106 H I CH2COOH .107 Cl I CH2COOH .108 F I CH2COOH .109 H CH3 CH2COOH .110 Cl CH3 CH2COOH .111 F CH3 CH2COOH .112 H OH CH2COOH .113 Cl OH CH2COOH .114 F OH CH2COOH .115 H OCF3 CH2COOH .116 Cl OCF3 CH2COOH .117 F OCF3 CH2COOH .118 H CHO CH2COOH .119 Cl CHO CH2COOH .120 F CHO CH2COOH .121 H CHF2 CH2COOH .122 Cl CHF2 CH2COOH .123 F CHF2 CH2COOH .124 H COOH CH2COOH .125 Cl COOH CH2COOH .126 F COOH CH2COOH .127 H COOCH2CH3 CH2COOH .128 Cl COOCH2CH3 CH2COOH .129 F COOCH2CH3 CH2COOH .130 H CN CH2COOH .131 Cl CN CH2COOH .132 F CN CH2COOH .133 H Cl CH2COOCH3 .134 Cl Cl CH2COOCH3 .135 F Cl CH2COOCH3 .136 H Br CH2COOCH3 .137 Cl Br CH2COOCH3 .138 F Br CH2COOCH3 .139 H I CH2COOCH3 .140 Cl I CH2COOCH3 .141 F I CH2COOCH3 .142 H CH3 CH2COOCH3 .143 Cl CH3 CH2COOCH3 .144 F CH3 CH2COOCH3 .145 H OH CH2COOCH3 .146 Cl OH CH2COOCH3 .147 F OH CH2COOCH3 .148 H OCF3 CH2COOCH3 .149 Cl OCF3 CH2COOCH3 .150 F OCF3 CH2COOCH3 .151 H CHO CH2COOCH3 .152 Cl CHO CH2COOCH3 .153 F CHO CH2COOCH3 .154 H CHF2 CH2COOCH3 .155 Cl CHF2 CH2COOCH3 .156 F CHF2 CH2COOCH3 .157 H COOH CH2COOCH3 .158 Cl COOH CH2COOCH3 .159 F COOH CH2COOCH3 .160 H COOCH2CH3 CH2COOCH3 .161 Cl COOCH2CH3 CH2COOCH3 .162 F COOCH2CH3 CH2COOCH3 .163 H CN CH2COOCH3 .164 Cl CN CH2COOCH3 .165 F CN CH2COOCH3 .166 H Cl OH .167 Cl Cl OH .168 F Cl OH .169 H Br OH .170 Cl Br OH .171 F Br OH .172 H I OH .173 Cl I OH .174 F I OH .175 H CH3 OH .176 Cl CH3 OH .177 F CH3 OH .178 H OH OH .179 Cl OH OH .180 F OH OH .181 H OCF3 OH .182 Cl OCF3 OH .183 F OCF3 OH .184 H CHO OH .185 Cl CHO OH .186 F CHO OH .187 H CHF2 OH .188 Cl CHF2 OH .189 F CHF2 OH .190 H COOH OH .191 Cl COOH OH .192 F COOH OH .193 H COOCH2CH3 OH .194 Cl COOCH2CH3 OH .195 F COOCH2CH3 OH .196 H CN OH .197 Cl CN OH .198 F CN OH .199 H Cl OCH2CHCH2 .200 Cl Cl OCH2CHCH2 .201 F Cl OCH2CHCH2 .202 H Br OCH2CHCH2 .203 Cl Br OCH2CHCH2 .204 F Br OCH2CHCH2 .205 H I OCH2CHCH2 .206 Cl I OCH2CHCH2 .207 F I OCH2CHCH2 .208 H CH3 OCH2CHCH2 .209 Cl CH3 OCH2CHCH2 .210 F CH3 OCH2CHCH2 .211 H OH OCH2CHCH2 .212 Cl OH OCH2CHCH2 .213 F OH OCH2CHCH2 .214 H OCF3 OCH2CHCH2 .215 Cl OCF3 OCH2CHCH2 .216 F OCF3 OCH2CHCH2 .217 H CHO OCH2CHCH2 .218 Cl CHO OCH2CHCH2 .219 F CHO OCH2CHCH2 .220 H CHF2 OCH2CHCH2 .221 Cl CHF2 OCH2CHCH2 .222 F CHF2 OCH2CHCH2 .223 H COOH OCH2CHCH2 .224 Cl COOH OCH2CHCH2 .225 F COOH OCH2CHCH2 .226 H COOCH2CH3 OCH2CHCH2 .227 Cl COOCH2CH3 OCH2CHCH2 .228 F COOCH2CH3 OCH2CHCH2 .229 H CN OCH2CHCH2 .230 Cl CN OCH2CHCH2 .231 F CN OCH2CHCH2 .232 H Cl OCH2C6H5 .233 Cl Cl OCH2C6H5 .234 F Cl OCH2C6H5 .235 H Br OCH2C6H5 .236 Cl Br OCH2C6H5 .237 F Br OCH2C6H5 .238 H I OCH2C6H5 .239 Cl I OCH2C6H5 .240 F I OCH2C6H5 .241 H CH3 OCH2C6H5 .242 Cl CH3 OCH2C6H5 .243 F CH3 OCH2C6H5 .244 H OH OCH2C6H5 .245 Cl OH OCH2C6H6 .246 F OH OCH2C6H5 .247 H OCF3 OCH2C6H5 .248 Cl OCF3 OCH2C6H5 .249 F OCF3 OCH2C6H5 .250 H CHO OCH2C6H5 .251 Cl CHO OCH2C6H5 .252 F CHO OCH2C6H5 .253 H CHF2 OCH2C6H5 .254 Cl CHF2 OCH2C6H5 .255 F CHF2 OCH2C6H5 .256 H COOH OCH2C6H5 .257 Cl COOH OCH2C6H5 .258 F COOH OCH2C6H5 .259 H COOCH2CH3 OCH2C6H5 .260 Cl COOCH2CH3 OCH2C6H5 .261 F COOCH2CH3 OCH2C6H5 .262 H CN OCH2C6H5 .263 Cl CN OCH2C6H5 .264 F CN OCH2C6H5 .265 H Cl OCH2COOH .266 Cl Cl OCH2COOH .267 F Cl OCH2COOH .268 H Br OCH2COOH .269 Cl Br OCH2COOH .270 F Br OCH2COOH .271 H I OCH2COOH .272 Cl I OCH2COOH .273 F I OCH2COOH .274 H CH3 OCH2COOH .275 Cl CH3 OCH2COOH .276 F CH3 OCH2COOH .277 H OH OCH2COOH .278 Cl OH OCH2COOH .279 F OH OCH2COOH .280 H OCF3 OCH2COOH .281 Cl OCF3 OCH2COOH .282 F OCF3 OCH2COOH .283 H CHO OCH2COOH .284 Cl CHO OCH2COOH .285 F CHO OCH2COOH .286 H CHF2 OCH2COOH .287 Cl CHF2 OCH2COOH .288 F CHF2 OCH2COOH .289 H COOH OCH2COOH .290 Cl COOH OCH2COOH .291 F COOH OCH2COOH .292 H COOCH2CH3 OCH2COOH .293 Cl COOCH2CH3 OCH2COOH .294 F COOCH2CH3 OCH2COOH .295 H CN OCH2COOH .296 Cl CN OCH2COOH .297 F CN OCH2COOH .298 H Cl OCH2COOCH3 .299 Cl Cl OCH2COOCH3 .300 F Cl OCH2COOCH3 .301 H Br OCH2COOCH3 .302 Cl Br OCH2COOCH3 .303 F Br OCH2COOCH3 .304 H I OCH2COOCH3 .305 Cl I OCH2COOCH3 .306 F I OCH2COOCH3 .307 H CH3 OCH2COOCH3 .308 Cl CH3 OCH2COOCH3 .309 F CH3 OCH2COOCH3 .310 H OH OCH2COOCH3 .311 Cl OH OCH2COOCH3 .312 F OH OCH2COOCH3 .313 H OCF3 OCH2COOCH3 .314 Cl OCF3 OCH2COOCH3 .315 F OCF3 OCH2COOCH3 .316 H CHO OCH2COOCH3 .317 Cl CHO OCH2COOCH3 .318 F CHO OCH2COOCH3 .319 H CHF2 OCH2COOCH3 .320 Cl CHF2 OCH2COOCH3 .321 F CHF2 OCH2COOCH3 .322 H COOH OCH2COOCH3 .323 Cl COOH OCH2COOCH3 .324 F COOH OCH2COOCH3 .325 H COOCH2CH3 OCH2COOCH3 .326 Cl COOCH2CH3 OCH2COOCH3 .327 F COOCH2CH3 OCH2COOCH3 .328 H CN OCH2COOCH3 .329 Cl CN OCH2COOCH3 .330 F CN OCH2COOCH3 .331 H Cl CH2CHO .332 Cl Cl CH2CHO .333 F Cl CH2CHO .334 H Br CH2CHO .335 Cl Br CH2CHO .336 F Br CH2CHO .337 H I CH2CHO .338 Cl I CH2CHO .339 F I CH2CHO .340 H CH3 CH2CHO .341 Cl CH3 CH2CHO .342 F CH3 CH2CHO .343 H OH CH2CHO .344 Cl OH CH2CHO .345 F OH CH2CHO .346 H OCF3 CH2CHO .347 Cl OCF3 CH2CHO .348 F OCF3 CH2CHO .349 H CHO CH2CHO .350 Cl CHO CH2CHO .351 F CHO CH2CHO .352 H CHF2 CH2CHO .353 Cl CHF2 CH2CHO .354 F CHF2 CH2CHO .355 H COOH CH2CHO .356 Cl COOH CH2CHO .357 F COOH CH2CHO .358 H COOCH2CH3 CH2CHO .359 Cl COOCH2CH3 CH2CHO .360 F COOCH2CH3 CH2CHO .361 H CN CH2CHO .362 Cl CN CH2CHO .363 F CN CH2CHO .364 H Cl OCH2CHO .365 Cl Cl OCH2CHO .366 F Cl OCH2CHO .367 H Br OCH2CHO .368 Cl Br OCH2CHO .369 F Br OCH2CHO .370 H I OCH2CHO .371 Cl I OCH2CHO .372 F I OCH2CHO .373 H CH3 OCH2CHO .374 Cl CH3 OCH2CHO .375 F CH3 OCH2CHO .376 H OH OCH2CHO .377 Cl OH OCH2CHO .378 F OH OCH2CHO .379 H OCF3 OCH2CHO .380 Cl OCF3 OCH2CHO .381 F OCF3 OCH2CHO .382 H CHO OCH2CHO .383 Cl CHO OCH2CHO .384 F CHO OCH2CHO .385 H CHF2 OCH2CHO .386 Cl CHF2 OCH2CHO .387 F CHF2 OCH2CHO .388 H COOH OCH2CHO .389 Cl COOH OCH2CHO .390 F COOH OCH2CHO .391 H COOCH2CH3 OCH2CHO .392 Cl COOCH2CH3 OCH2CHO .393 F COOCH2CH3 OCH2CHO .394 H CN OCH2CHO .395 Cl CN OCH2CHO .396 F CN OCH2CHO .397 H Cl OCH3 .398 Cl Cl OCH3 .399 F Cl OCH3 .400 H Br OCH3 .401 Cl Br OCH3 .402 F Br OCH3 .403 H I OCH3 .404 Cl I OCH3 .405 F I OCH3 .406 H CH3 OCH3 .407 Cl CH3 OCH3 .408 F CH3 OCH3 .409 H OH OCH3 .410 Cl OH OCH3 .411 F OH OCH3 .412 H OCF3 OCH3 .413 Cl OCF3 OCH3 .414 F OCF3 OCH3 .415 H CHO OCH3 .416 Cl CHO OCH3 .417 F CHO OCH3 .418 H CHF2 OCH3 .419 Cl CHF2 OCH3 .420 F CHF2 OCH3 .421 H COOH OCH3 .422 Cl COOH OCH3 .423 F COOH OCH3 .424 H COOCH2CH3 OCH3 .425 Cl COOCH2CH3 OCH3 .426 F COOCH2CH3 OCH3 .427 H CN OCH3 .428 Cl CN OCH3 .429 F CN OCH3 .430 H Cl CH2OCH3 .431 Cl Cl CH2OCH3 .432 F Cl CH2OCH3 .433 H Br CH2OCH3 .434 Cl Br CH2OCH3 .435 F Br CH2OCH3 .436 H I CH2OCH3 .437 Cl I CH2OCH3 .438 F I CH2OCH3 .439 H CH3 CH2OCH3 .440 Cl CH3 CH2OCH3 .441 F CH3 CH2OCH3 .442 H OH CH2OCH3 .443 Cl OH CH2OCH3 .444 F OH CH2OCH3 .445 H OCF3 CH2OCH3 .446 Cl OCF3 CH2OCH3 .447 F OCF3 CH2OCH3 .448 H CHO CH2OCH3 .449 Cl CHO CH2OCH3 .450 F CHO CH2OCH3 .451 H CHF2 CH2OCH3 .452 Cl CHF2 CH2OCH3 .453 F CHF2 CH2OCH3 .454 H COOH CH2OCH3 .455 Cl COOH CH2OCH3 .456 F COOH CH2OCH3 .457 H COOCH2CH3 CH2OCH3 .458 Cl COOCH2CH3 CH2OCH3 .459 F COOCH2CH3 CH2OCH3 .460 H CN CH2OCH3 .461 Cl CN CH2OCH3 .462 F CN CH2OCH3 .463 H Cl CH2SCH3 .464 Cl Cl CH2SCH3 .465 F Cl CH2SCH3 .466 H Br CH2SCH3 .467 Cl Br CH2SCH3 .468 F Br CH2SCH3 .469 H I CH2SCH3 .470 Cl I CH2SCH3 .471 F I CH2SCH3 .472 H CH3 CH2SCH3 .473 Cl CH3 CH2SCH3 .474 F CH3 CH2SCH3 .475 H OH CH2SCH3 .476 Cl OH CH2SCH3 .477 F OH CH2SCH3 .478 H OCF3 CH2SCH3 .479 Cl OCF3 CH2SCH3 .480 F OCF3 CH2SCH3 .481 H CHO CH2SCH3 .482 Cl CHO CH2SCH3 .483 F CHO CH2SCH3 .484 H CHF2 CH2SCH3 .485 Cl CHF2 CH2SCH3 .486 F CHF2 CH2SCH3 .487 H COOH CH2SCH3 .488 Cl COOH CH2SCH3 .489 F COOH CH2SCH3 .490 H COOCH2CH3 CH2SCH3 .491 Cl COOCH2CH3 CH2SCH3 .492 F COOCH2CH3 CH2SCH3 .493 H CN CH2SCH3 .494 Cl CN CH2SCH3 .495 F CN CH2SCH3 .496 H Cl OCH2OCH3 .497 Cl Cl OCH2OCH3 .498 F Cl OCH2OCH3 .499 H Br OCH2OCH3 .500 Cl Br OCH2OCH3 .501 F Br OCH2OCH3 .502 H I OCH2OCH3 .503 Cl I OCH2OCH3 .504 F I OCH2OCH3 .505 H CH3 OCH2OCH3 .506 Cl CH3 OCH2OCH3 .507 F CH3 OCH2OCH3 .508 H OH OCH2OCH3 .509 Cl OH OCH2OCH3 .510 F OH OCH2OCH3 .511 H OCF3 OCH2OCH3 .512 Cl OCF3 OCH2OCH3 .513 F OCF3 OCH2OCH3 .514 H CHO OCH2OCH3 .515 Cl CHO OCH2OCH3 .516 F CHO OCH2OCH3 .517 H CHF2 OCH2OCH3 .518 Cl CHF2 OCH2OCH3 .519 F CHF2 OCH2OCH3 .520 H COOH OCH2OCH3 .521 Cl COOH OCH2OCH3 .522 F COOH OCH2OCH3 .523 H COOCH2CH3 OCH2OCH3 .524 Cl COOCH2CH3 OCH2OCH3 .525 F COOCH2CH3 OCH2OCH3 .526 H CN OCH2OCH3 .527 Cl CN OCH2OCH3 .528 F CN OCH2OCH3 .529 H Cl OCH2SCH3 .530 Cl Cl OCH2SCH3 .531 F Cl OCH2SCH3 .532 H Br OCH2SCH3 .533 Cl Br OCH2SCH3 .534 F Br OCH2SCH3 .535 H I OCH2SCH3 .536 Cl I OCH2SCH3 .537 F I OCH2SCH3 .538 H CH3 OCH2SCH3 .539 Cl CH3 OCH2SCH3 .540 F CH3 OCH2SCH3 .541 H OH OCH2SCH3 .542 Cl OH OCH2SCH3 .543 F OH OCH2SCH3 .544 H OCF3 OCH2SCH3 .545 Cl OCF3 OCH2SCH3 .546 F OCF3 OCH2SCH3 .547 H CHO OCH2SCH3 .548 Cl CHO OCH2SCH3 .549 F CHO OCH2SCH3 .550 H CHF2 OCH2SCH3 .551 Cl CHF2 OCH2SCH3 .552 F CHF2 OCH2SCH3 .553 H COOH OCH2SCH3 .554 Cl COOH OCH2SCH3 .555 F COOH OCH2SCH3 .556 H COOCH2CH3 OCH2SCH3 .557 Cl COOCH2CH3 OCH2SCH3 .558 F COOCH2CH3 OCH2SCH3 .559 H CN OCH2SCH3 .560 Cl CN OCH2SCH3 .561 F CN OCH2SCH3 .562 H Cl OCH2CH2CN .563 Cl Cl OCH2CH2CN .564 F Cl OCH2CH2CN .565 H Br OCH2CH2CN .566 Cl Br OCH2CH2CN .567 F Br OCH2CH2CN .568 H I OCH2CH2CN .569 Cl I OCH2CH2CN .570 F I OCH2CH2CN .571 H CH3 OCH2CH2CN .572 Cl CH3 OCH2CH2CN .573 F CH3 OCH2CH2CN .574 H OH OCH2CH2CN .575 Cl OH OCH2CH2CN .576 F OH OCH2CH2CN .577 H OCF3 OCH2CH2CN .578 Cl OCF3 OCH2CH2CN .579 F OCF3 OCH2CH2CN .580 H CHO OCH2CH2CN .581 Cl CHO OCH2CH2CN .582 F CHO OCH2CH2CN .583 H CHF2 OCH2CH2CN .584 Cl CHF2 OCH2CH2CN .585 F CHF2 OCH2CH2CN .586 H COOH OCH2CH2CN .587 Cl COoH OCH2CH2CN .588 F COOH OCH2CH2CN .589 H COOCH2CH3 OCH2CH2CN .590 Cl COOCH2CH3 OCH2CH2CN .591 F COOCH2CH3 OCH2CH2CN .592 H CN OCH2CH2CN .593 Cl CN OCH2CH2CN .594 F CN OCH2CH2CN .595 H Cl CH2CH2CN .596 Cl Cl CH2CH2CN .597 F Cl CH2CH2CN .598 H Br CH2CH2CN .599 Cl Br CH2CH2CN .600 F Br CH2CH2CN .601 H I CH2CH2CN .602 Cl I CH2CH2CN .603 F I CH2CH2CN .604 H CH3 CH2CH2CN .605 Cl CH3 CH2CH2CN .606 F CH3 CH2CH2CN .607 H OH CH2CH2CN .608 Cl OH CH2CH2CN .609 F OH CH2CH2CN .610 H OCF3 CH2CH2CN .611 Cl OCF3 CH2CH2CN .612 F OCF3 CH2CH2CN .613 H CHO CH2CH2CN .614 Cl CHO CH2CH2CN .615 F CHO CH2CH2CN .616 H CHF2 CH2CH2CN .617 Cl CHF2 CH2CH2CN .618 F CHF2 CH2CH2CN .619 H COOH CH2CH2CN .620 Cl COOH CH2CH2CN .621 F COOH CH2CH2CN .622 H COOCH2CH3 CH2CH2CN .623 Cl COOCH2CH3 CH2CH2CN .624 F COOCH2CH3 CH2CH2CN .625 H CN CH2CH2CN .626 Cl CN CH2CH2CN .627 F CN CH2CH2CN
[0526] 201 TABLE E Prepared compounds from the above Tables with physicochemical data. The numbers in front of the point designates the number of the Table e.g. 1.150 signifies in Table 1 the compound No. 150 of Table A and 72.133 signifies in Table 72 the compound No. 133 of Table B. Compd. No. Physicochemical data 1.001 m.p. 137-139° C. 1.002 m.p. 142-146° C. 1.003 m.p. 122-124° C. 1.004 amorphous (Example P45) 1.007 solid 1.010 resin 1.015 m.p. 76-78° C. 1.031 m.p. 88-90° C. 1.045 m.p. 85-86° C. 1.080 resin (Example P44) 1.100 m.p. 104-105° C. 1.105 m.p. 105-107° C. 1.106 resin 1.111 m.p. 93-94° C. 1.126 m.p. 104-106° C. 1.137 m.p. 89-93° C. 1.147 resin (Example P51) 1.150 m.p. 137-138° C. 1.152 m.p. 167-168° C. 1.153 m.p. 171-172° C. (Example P52) 1.155 m.p. 102-104° C. 1.156 m.p. 113-114° C. 1.161 m.p. 143-145° C. (Example P53) 1.162 m.p. 180-182° C. 1.168 m.p. 122-124° C. 1.177 solid (Example P47) 1.181 amorphous 1.182 m.p. 98-100° C. 1.190 oil 1.195 m.p. 83-85° C. (Example P46) 1.205 resin 1.216 m.p. 80-86° C. 1.234 amorphous (Example P49) 1.244 m.p. 146-148° C. (Example P50) 1.294 oil (Example P55) 1.302 m.p. 102-104° C. 1.397 resin (Example P32) 1.400 resin (Example P33) 1.422 m.p. 100-101° C. 1.494 m.p. 135-138° C. (Example P54) 7.100 m.p. 111-113° C. 9.002 resin 9.100 m.p. 110-112° C. 10.100 m.p. 126-127° C. 22.002 m.p. 131-133° C. 22.100 m.p. 190-191° C. (Example P43) 28.100 m.p. 189-192° C. (Example P42) 72.083 m.p. 152-153° C. (Example P60) 72.113 m.p. 250° C. (decomposition) (Example P59) 72.133 m.p. 140-143° C. (Example P58)
[0527] Examples of specific formulations of the compounds of formula 1, such as emulsifiable concentrates, solutions, wettable powders, coated granules, extruder granules, dusts and suspension concentrates, are described in WO 97/34485, pages 9 to 13.
BIOLOGICAL EXAMPLES Example B1: Herbicidal action prior to emergence of the plants (pre-emergence action)[0528] Monocotyledonous and dicotyledonous test plants are sown in standard soil in plastics pots. Immediately after sowing, the test compounds, each in the form of an aqueous suspension or emulsion prepared from a 25% emulsifiable concentrate (Example F1, c) in WO 97/34485, pages 9 and 10), are applied by spraying at a rate of application of 2000 g of active ingredient/ha (500 liters water/ha). The test plants are then grown in a greenhouse under optimum conditions. After 3 weeks' test duration, the test is evaluated in accordance with a scale of nine ratings (1=total damage, 9=no action). Ratings of from 1 to 4 (especially from 1 to 3) indicate good to very good herbicidal action.
[0529] Test plants: Avena, Setaria, Sinapis, Stellaria
[0530] The compounds according to the invention exhibit a good herbicidal action.
[0531] Examples of the good herbicidal activity of the compounds of formula I are given in Table B1. 202 TABLE B1 Pre-emergence action: Test plant Concentration Compd. No. Avena Setaria Sinapis Stellaria [g a.i./ha] 1.001 1 1 1 1 2000 1.002 1 1 1 1 2000 1.003 1 1 1 1 2000 1.004 1 1 1 1 2000 1.010 1 1 1 1 2000 1.080 1 1 1 1 2000 1.100 1 1 1 1 2000 1.105 1 1 1 1 2000 1.106 2 1 1 1 2000 1.111 2 1 1 1 2000 1.126 1 1 1 1 2000 1.147 1 1 1 1 2000 1.150 1 1 1 1 2000 1.152 1 1 1 1 2000 1.153 1 1 1 1 2000 1.156 1 1 1 1 2000 1.168 1 1 1 1 2000 1.181 1 1 1 1 2000 1.190 2 1 1 1 2000 1.195 3 1 1 1 2000 1.205 1 1 1 1 2000 1.302 1 1 1 1 2000 1.400 1 1 1 1 2000 7.100 1 1 1 1 2000 9.002 1 3 1 1 2000 9.100 1 1 1 1 2000 10.100 1 1 1 1 2000 28.100 1 1 1 1 2000
[0532] The same results are obtained when compounds of formula I are formulated according to Examples F2 to F8 in WO 97/34485, pages 10 to 12.
Example B2: Post-emergence herbicidal action[0533] Monocotyledonous and dicotyledonous test plants are grown in a greenhouse in plastics pots containing standard soil and at the 4- to 6-leaf stage are sprayed with an aqueous suspension or emulsion of the test substances of formula I, prepared from a 25% emulsifiable concentrate (Example F1, c) in WO 97/34485, pages 9 and 10), at a rate of application corresponding to 2000 g of active ingredient/ha (500 liters water/ha). The test plants are then grown on in the greenhouse under optimum conditions. After approximately 18 days' test duration, the test is evaluated in accordance with a scale of nine ratings (1=total damage, 9=no action). Ratings of from 1 to 4 (especially from 1 to 3) indicate good to very good herbicidal action.
[0534] Test plants: Avena, Setaria, Sinapis, Stellaria
[0535] In this test, too, the compounds of formula I exhibit a strong herbicidal action.
[0536] Examples of the good herbicidal activity of the compounds of formula I are given in Table B2 203 TABLE B2 Post-emergence action: Test plant Concentration Compd. No. Avena Setaria Sinapis Stellaria [g a.i./ha] 1.001 1 1 1 1 2000 1.002 1 1 1 1 2000 1.003 1 1 1 1 2000 1.004 1 2 1 1 2000 1.010 1 1 1 1 2000 1.080 1 1 1 1 2000 1.100 1 1 1 1 2000 1.105 1 2 1 1 2000 1.106 3 3 1 1 2000 1.111 2 1 1 2 2000 1.126 1 1 1 1 2000 1.147 1 1 1 1 2000 1.150 1 1 1 1 2000 1.152 1 1 1 1 2000 1.153 1 1 1 1 2000 1.156 1 1 1 1 2000 1.168 1 1 1 1 2000 1.181 1 1 1 1 2000 1.190 1 1 1 1 2000 1.195 1 1 1 1 2000 1.205 1 1 1 1 2000 1.302 1 1 1 1 2000 1.400 1 2 1 1 2000 7.100 1 1 1 1 2000 9.002 1 3 1 1 2000 9.100 2 2 1 1 2000 10.100 1 2 1 1 2000 28.100 1 1 1 1 2000
[0537] The same results are obtained when the compounds of formula I are formulated according to examples F2 to F8 in WO 97/34485, pages 10 to 12.
Claims
1. A compound of formula I
- 314
- R1 is hydrogen, C1-C4alkyl, C1-C4haloalkyl, cyano-C1-C4alkyl, C3- or C4-alkenyl, C3- or C4-haloalkenyl, C3- or C4-alkynyl or C3-C6cycloalkyl;
- R2 is hydrogen, C1-C4alkyl, C1-C4haloalkyl, C3-C6alkenyl, C3-C6haloalkenyl, C3-C6alkynyl, C1-C4alkyl-S(O)2— or C1-C4haloalkyl-S(O)2—;
- R 3 is hydrogen, C1-C4alkyl, C1-C4haloalkyl, C2-C6alkenyl, C2-C6haloalkenyl, C2-C6alkynyl, halogen, cyano, NH2C(S)—, nitro or amino;
- n1 is 0, 1 or 2;
- R4 is hydrogen, C1-C4alkyl, C1-C4haloalkyl, C3-C6alkenyl, C3-C6haloalkenyl, C3-C6alkynyl or C3-C6cycloalkyl;
- R5 is hydrogen, halogen, C1-C4alkyl, C1-C4haloalkyl, cyano, nitro, amino, NH2C(O)—, NH2C(S)—, C1-C4alkylcarbonyl, C1-C6alkoxycarbonyl, C1-C4haloalkylcarbonyl, C2 -C4alkenylcarbonyl, C1-C3alkyl-CH(OH)—, OHC—, HOC(O)—, CIC(O)—, HON═CH—, C1-C4alkoxy-N═CH—, C2-C4haloalkenylcarbonyl or C2-C4alkynylcarbonyl;
- R11 is hydrogen, fluorine, chlorine, bromine or methyl;
- R12 is hydrogen, halogen, methyl, halomethyl, nitro, amino, hydroxy, OHC—, HOC(O)—, cyano, C1-C4alkoxycarbonyl or halomethoxy;
- X1 is O, S, R20N═ or R25ON═;
- R13 is hydroxy, C1-C6alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6haloalkoxy, C3-C6-haloalkenyloxy, C1-C6alkoxy-C1-C6alkyl, C3-C6alkenyloxy-C1-C6alkyl, C3-C6alkynyloxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkyl, B1-C1-C6alkoxy, R21(R22)N—, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C2-C6haloalkyl, C3-C6haloalkenyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, B1-C1-C6alkyl, OHC—, C1-C6alkylcarbonyl, C1-C6alkylcarbonyloxy, C1-C6haloalkylcarbonyl, C2-C6alkenylcarbonyl, C1-C6alkoxycarbonyl, C1-C6alkyl-S(O)2—, C1-C6haloalkyl-S(O)2-, (C1-C6alkyl)2N—N═CH—,
- 315
- B1-CH═N—, (CH3)2N—CH═N—, (C1-C5hydroxyalkyl)-CH2—, (B1-C1-C5hydroxyalkyl)-CH2—, (B1-C1-C5haloalkyl)-CH2—, (hydroxy-C1-C5alkyl)-O— or (B1-C1-C5hydroxyalkyl)-O—;
- B1 is cyano, OHC—, HOC(O)—, C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, C3-C6alkenyloxycarbonyl, C3-C6alkynyloxycarbonyl, benzyloxycarbonyl, benzyloxycarbonyl mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl, benzylthiocarbonyl, benzylthiocarbonyl mono- to tri-substituted at the phenyl ring by halogen, C1-C4-alkyl or by C1-C4haloalkyl, C1-C6haloalkoxycarbonyl, C1-C6alkylthio-C(O)—, R26(R27)NC(O)—, phenyl, phenyl mono- to tri-substituted by halogen, C1-C4alkyl or by C1-C4haloalkyl, C1-C6-alkyl-S(O)2—, C1-C6alkyl-S(O)—, C1-C6alkylthio, C3-C6cycloalkyl, C1-C6alkoxy, C3-C6alkenylthio or C3-C6alkynylthio;
- R20 is hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C2-C6haloalkyl, cyano, R23(R24)N—, C1-C6alkoxycarbonyl, C3-C6alkenyloxycarbonyl, C3-C6alkynyloxycarbonyl, C2-C6haloalkoxycarbonyl, OHC—, C1-C6alkylcarbonyl, C1-C6haloalkylcarbonyl, C1-C6alkyl-S(O)2—, C1-C6haloalkyl-S(O)2—, phenyl, phenyl mono- to tri-substituted by halogen, C1-C4alkyl or by C1-C4haloalkyl, phenyl-C1-C6alkyl, or phenyl-C1-C6alkyl mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl;
- R21 and R22 are each independently hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6-haloalkyl, C3-C6haloalkenyl, C3-C6cycloalkyl, C1-C6alkoxy-C1-C6alkyl, OHC—, C1-C6alkylcarbonyl, C1-C6haloalkylcarbonyl, C1-C6alkyl-S(O)2— or C1-C6haloalkyl-S(O)2—;
- R23 and R24 are each independently as defined for R21;
- R25 is hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C3-C6haloalkenyl, C1-C6alkoxy-C1-C6alkyl, benzyl, C1-C6alkyl-S(O)2— or C1-C6haloalkyl-S(O)2—;
- R26 and R27 are each independently hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C3-C6haloalkenyl, phenyl, phenyl mono- to tri-substituted by halogen, C1-C4alkyl or by C1-C4haloalkyl, benzyl, or benzyl mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl; or
- X1 and R13 together form a group ═N—Y— wherein Y is bonded to the ring nitrogen atom;
- Y is —C(R31)(R32)—CH2—, —C(R31)(R32)—O—, —C(R31)(R32)—CH2—CH2—, —C(R31)(R32)—CH2—O—, —O—CH2—, —O—CH2—CH2—, —O—CH═CH—, —N(R33)—CH2—, —N(R33)—CH2—CH2—, —N(R33)—CH═CH—, —N(R33)—C(X3)—CH2—, —C(X3)—CH2—, —C(X3)—CH2—CH2—, —C(X3)—CH2—O—, —C(X3)—O—, —C(R34)═CH—, —C(R31)(R32)—CH═CH—, —C(R34)═N—, —C(R31)(R32)—CH═N—, —C(R31)(R32)—N═CH—, —C(X3)—CH═CH—, —N═N—, —C(R31)(R32)—C(O)—, —C(R31)(R32)—C(S)—, —C(R31)(R32)—CH2—C(O)—, —C(R31)(R32)—CH2—C(S)—, —N(R33)—C(O)—, —N(R33)—C(S)—, —N(R33)—CH2—C(O)—, —N(R33)—CH2—C(S)—, —O—C(O)—, —O—C(S)—, —C(R34)═CH—C(O)— or —C(R34)═CH—C(S)—, the right-hand end of the bridge members in the above definitions of Y being bonded to the ring nitrogen atom;
- R31 is hydrogen, C1-C6alkyl or C1-C6haloalkyl;
- R32 is hydrogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl, cyano-C1-C6alkyl, hydroxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C3-C6alkenyloxy-C1-C6alkyl, C3-C6alkynyloxy-C1-C6alkyl, C1-C6alkylcarbonyloxy-C1-C6alkyl, C1-C6haloalkylcarbonyloxy-C1-C6alkyl, carboxyl, C1-C6alkoxycarbonyl, C3-C6alkenyloxycarbonyl, C3-C6alkynyloxycarbonyl, C1-C6haloalkoxycarbonyl, C3-C6cycloalkoxycarbonyl, C1-C4alkoxy-C1-C6alkoxycarbonyl, C1-C6alkyl-NHC(O)—, (C1-C6alkyl)2NC(O)—, C3-C6alkenyl-NHC(O)—, C1-C6alkyl-(C3-C6-alkenyl)NC(O)—, C3-C6alkynyl-NHC(O)—, aminocarbonyl, C1-C6alkylthio-C(O)—, C3-C6-alkenylthio-C(O)—, C3-C6alkynylthio-C(O)—, benzyloxycarbonyl, benzyloxycarbonyl mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl, phenoxycarbonyl, C1-C6alkyl-S(O)2NHC(O)—, C1-C6alkyl-S(O)2(C3-C6alkenyl)N—C(O)—, C1-C6haloalkyl-S(O)2NHC(O)—, HON═CH—, C1-C6alkoxy-N═CH—, C3-C6alkenyloxy-N═CH—, C3-C6alkynyloxy-N═CH—, HOC(O)—C1-C6alkyl, C1-C6alkoxycarbonyl-C1-C6alkyl, C3-C6alkenyloxycarbonyl-C1-C6alkyl, C3-C6alkynyloxycarbonyl-C1-C6alkyl, C1-C6alkylcarbonyl, CIC(O)—, H2NC(S)—, OHC—, cyano, phenyl, phenyl mono- to tri-substituted by halogen, C1-C4alkyl or by C1-C4-haloalkyl, phenyl-C1-C6alkyl, or phenyl-C1-C6alkyl mono- to tri-substituted at the phenyl ring by halogen, C1-C4alkyl or by C1-C4haloalkyl;
- X3 is O, S, R20N═ or R25ON═;
- R33 is hydrogen, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C3-C6haloalkenyl, C3-C6cycloalkyl, C1-C6alkylcarbonyl, C1-C6haloalkylcarbonyl, C1-C6alkyl-S(O)2— or B2-C1-C6-alkyl;
- B2 is cyano, HOC(O)—, C1-C6alkoxycarbonyl, C1-C6alkylcarbonyl or C1-C6alkoxy; and
- R34 is as defined for R32 or is halogen, C1-C6alkoxy, C3-C6alkenyloxy, C1-C6haloalkoxy, C1-C6alkylthio, C1-C6alkyl-S(O)— or C1-C6alkyl-S(O)2—,
- or a pyrazole N-oxide, an agrochemically acceptable salt or a stereoisomer of that compound of formula I.
2. A compound of formula I according to claim 1 having the formula Ia
- 316
- R1, R2, R3, R4, R5, R11, R12, R13, X1 and n1 are as defined in claim 1.
3. A process for the preparation of a compound of formula I
- 317
- wherein R11, R12 and W are as defined in claim 1; X1 is O or S; R13 is C1-C6alkoxy-C1-C6-alkyl, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkyl, C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C2-C6-haloalkyl, C3-C6haloalkenyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, B1-C1-C6alkyl,
- 318
- (C1-C5hydroxyalkyl)-CH2—, (B1-C1-C5hydroxyalkyl)-CH2— or (B1-C1-C5haloalkyl)-CH2—; and B1is as defined in claim 1, which comprises oxidising a compound of formula III
- 319
- in a suitable solvent to form a compound of formula V
- 320
- and subsequently rearranging that compound in an inert solvent in the presence of an anhydride or in the presence of antimony pentachloride to yield, after aqueous working up, a compound of formula II
- 321
- the radicals R11, R12 and W in the compounds of formulae II, III and V being as defined above, and then alkylating that compound in the presence of an inert solvent and a base with a compound of formula VI
- R13—L (VI),
- wherein R13 is as defined above and L is a leaving group, to form the compounds of formulae I and IV
- 322
- wherein R11, R12, R13 and W are as defined above and X1 is O, and subsequently, where appropriate after separating off the compound of formula I, functionalising the pyridone group thereof according to the definition of X1 and R13.
4. A process for the preparation of a compound of formula I
- 323
- wherein R11, R12 and W are as defined in claim 1; X1 is S; R13 is hydroxy, C1-C6alkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C6haloalkoxy, C3-C6haloalkenyloxy, B1-C1-C6alkoxy, C1-C6alkylcarbonyl, C1-C6alkylcarbonyloxy, C1-C6haloalkylcarbonyl, C2-C6alkenylcarbonyl or C1-C6alkoxycarbonyl; and B1 is as defined in claim 1, which comprises first of all oxidising a compound of formula III
- 324
- to yield a compound of formula V
- 325
- chlorinating or brominating that compound to form a compound of formula VIII
- 326
- the radicals R11, R12 and W in the compounds of formulae III, V and VIII being as defined above and Hal in the compound of formula VIII being chlorine or bromine, subsequently converting the compound of formula VII with a suitable sulfur reagent into a compound of formula Ic
- 327
- and reacting that compound in the presence of a solvent and a base with a compound of formula XI
- R14—L (XI),
- wherein R14 is C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C3-C6haloalkenyl, B1-C1-C6alkyl or C1-C6alkylcarbonyl; B1 is as defined above; and L is a leaving group.
5. A compound of formula VIII
- 328
- wherein R11, R12 and W are as defined in claim 1 and Hal is chlorine or bromine.
6. A herbicidal and plant-growth-inhibiting composition having a herbicidally effective content of a compound of formula I according to claim 1 and comprising an inert carrier.
7. A composition according to claim 6 comprising from 0.1% to 95% of a compound of formula I.
8. A method of controlling undesired plant growth, which comprises applying a compound of formula I, or a composition comprising that compound, in a herbicidally effective amount to the crops of useful plants or to the locus thereof.
9. The use of a composition according to claim 6 in the control of undesired plant growth.
Type: Application
Filed: Jun 14, 2001
Publication Date: May 9, 2002
Inventors: Kurt Nebel (Hochwald), Alain De Mesmaeker (Kaenerkinden), Jurgen Schaetzer (Rheinfelden)
Application Number: 09881160
International Classification: C 07D 4 3/04;
