Abstract: The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester In accordance with the present invention, a pharmaceutical grade Compound (I) can be efficiently prepared by a one-pot reactions preparation step that includes the esterification of the 15-OH bimatoprost by coupling bimatoprost phenyl-boronate with 6-(nitrooxy)hexanoic acid and the removal of the boronate ester protecting group, followed by an efficient purification step. The invention refers also to high purity Compound (I) substantially free of the impurity 15-(6-chlorohexanoyl) ester of bimatoprost and to ophthalmic pharmaceutical formulations containing the high purity compound.

Abstract: The present invention relates to a process for the preparation of a chiral prostaglandin enol intermediate of formula 1, comprising the steps of: separating a compound of formula 16-(R,S)-10 into its diastereomers by fractional crystallisation, reducing the 15-oxo group of the compound of formula 16-(R)-10, thereby obtaining a compound of formula 15-(R,S), 16-(R)-11, followed by removing the protecting group of the compound of formula 15-(R,S), 16-(R)-11, and isolating the compound of formula 1, and optionally, crystallizing the compound of formula 1. Optionally, the undesired isomer formed during fractional crystallization can be epimerized and further amount of the desired isomer can be recovered from the resulting mixture. The present invention also provides novel intermediates useful in the process. The invention further relates to a process for fractional crystallization of the compound of formula 16-(R,S)-10.

Abstract: The invention relates to a process for the preparation of a compound of the formula (I) by reacting a compound of the formula (II) with a compound of the formula (III) characterized by dissolving the compounds of the formula (II) and formula (III) in a water-inmiscible organic solvent in the presence of a phase transfer catalyst, reacting with a.) an aqeuos solution of a base, or b.) a base in solid form directly and if desired transforming the compound of formula (I) thus obtained into its salt.

Abstract: The invention relates to a process for the preparation of spiro[(4-cyclohexanone)-[3H]indol]-2?[1?H]-one derivatives of the general formula I wherein R1 and R2 independently stand for hydrogen, C1-4alkyl, C1-4alkoxy, C1-4alkylthio, C1-4polyfluoroalkyl, C1-4polyfluoroalkoxy, C3-7cycloalkyloxy, C3-7cycloalkylthio, phenoxy, benzyloxy or nitro group—, characterized by reacting an indolin-2-one derivative of the general formula II wherein R1 and R2 are as defined above—with a compound capable for introducing a protective group, selected from 2-tetrahydropyranyl, 1-diethoxy-methylene or C1-4alkoxycarbonylethyl group, coupling the compound of general formula III, thus obtained—wherein R1 and R2 are as defined above and A stands for a protective group, selected from 2-tetrahydropyranyl, 1-diethoxy-methylene or C1-4alkoxycarbonylethyl group—with an acrylic acid C1-4ester, cyclizing the resulting compound of the general formula IV wherein R1, R2 and A are as defined above, R3 stands for C1-4 alkyl grou

Abstract: New process for the preparation of 1,5-disubstituted-3-amino-1,2,4-triazoles of the general formula (I), wherein the meaning of R is C1-5alkyl group; C3-13cycloalkyl-C0-4alkyl group, optionally substituted by one or more C1-3alkyl group; phenyl-C0-2alkyl-, (CH2)n-morpholino-, piperidino-, pyrrolidino- or piperazino-group, optionally substituted by one or more halogen atom, C1-3alkyl group, C1-3alkoxy group, n is 1-5, R1, R2, R3, and R4 stand independently for hydrogen, halogen, C1-6alkyl group, C1-3alkoxy group or trifuluoromethyl group, with the proviso that of the substituents R1, R2, R3, and R4 at least one stands for hydrogen.

Abstract: The invention relates to a process for the preparation of spiro[(4-cyclohexanone)-[3H]indol]-2′[1′H]-one derivatives of the general formula I 1

Abstract: The invention relates to a process for the preparation of a compound of formula (I) and the salts thereof by reacting the compound of formula (II) with the compound of formula (III), which comprises carrying out the reaction in dimethyl sulfoxide, at a temperature between 10° C. and 40° C., preferably at room temperature and transforming the resulting base of formula (I), if desired, into its salt by a method known per se.

Abstract: The invention relates to a process for the preparation of spiro [(4-cyclohexanone)-[3H]indol]-2′[1′H]-one derivatives of general formula I—wherein R1 and R2 independently stand for hydrogen, C1-4alkyl, C1-4alkoxy, C1-4alkylthio, C1-4polyfluoroalkyl, C1-4polyfluoroalkoxy, C3-7cycloalkyloxy, C3-7cycloalkylthio, phenoxy, benzyloxy or nitro group—, characterized by reacting an indolin-2-one derivative of general formula II—wherein R1 and R2 are as defined above—with a compound capable for introducing a protective group, coupling the compound of general formula III, thus obtained—wherein R1 and R2 are as defined above and A stands for a protective group—with acrylic acid C1-4ester; cyclizing the resulting compound of general formula IV—wherein R1 and R2 are as defined above—with a compound capable for introducing a protective group, coupling the compound of formula III thus obtained,—wherein R1 and R2 are as defined abo

Abstract: The invention relates to a process for the preparation of 2-methoxy-4-(N-t-butylaminocarbonyl)benzenesulfonyl chloride by sulfonating m-hydroxybenzoic acid, methylating the hydroxy group of the resulting sulfonic acid or its salt, transforming the carboxylic acid group and the sulfonic acid group to acid chloride groups and reacting the 4-chlorosulfonyl-3-methoxy-benzoyl chloride with t-butylamine, which comprises carrying out the sulfonation of the 3-methoxy-benzoic acid of general formula (II) with 96% sulfuric acid, separating the resulting 3-hydroxy-4-sulfobenzoic acid of general formula (III) in the form of its salt of general formula (IV), wherein Z stands for alkali metal or ammonium group, methylating the compound of general formula (IV) in the presence of a phase transfer catalyst at a pH value of about 11.

Abstract: The invention relates to a process for the preparation of spiro[cis-4-(&bgr;-hydroxyethyloxy)cyclohexane-[3H]indol]-2′[1′H]-one derivatives of the formula (I) wherein R1 and R2 are as defined herein, by reduction of a dispiro[(1,3-dioxolane)-2,4′-cyclohexane-1′3′-[3H]indol]-2″[1″H]-one derivative of general formula (II), wherein R1 and R2 are as defined herein, which comprises carrying out the reduction (a) with sodium cyanoborohydride in the presence of a Lewis acid, or (b) with sodium borohydride in the presence of a strong acid.

Abstract: The invention relates to novel diphenylpropylamine derivatives of the general formula (I). ##STR1## R.sup.1 stands for hydrogen or a methyl group; R.sup.2 stands for hydrogen, a methyl or n-decyl group;Z means a phenyl group substituted by R.sup.3, R.sup.4 and R.sup.5, whereinR.sup.3 means hydrogen, fluorine, chlorine or bromine, or a nitro, C.sub.1-12 alkyl, C.sub.1-4 alkoxy, phenoxy or benzyloxy group;R.sup.4 and R.sup.5 represent hydrogen, chlorine or a hydroxy, alkoxy, benzyloxy, acetamino or carboxy group; orR.sup.4 and R.sup.5 together form a methylendioxy group;orZ may stand for a 4-methoxynaphtyl or 4-ethoxy-naphthyl group; andR.sup.6 stands for hydrogen or fluorine, with the proviso that each of R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.6 cannot simultaneously stand for hydrogen, as well as their physiologically acceptable acid addition salts.The invention also relates to a process for the preparation of these compounds and to the pharmaceutical compositions containing these compounds.