Patent ID: 6835843
Filing Date: 2004-12-28
Classification: A61K,C07D,C07K

Abstract:
A process for the industrial synthesis of perindopril of formula (I) or a pharmaceutically acceptable salts thereof, wherein the benzyl ester of formula (IV): in which Bn represents benzyl, is reacted with the compound of formula (V): in ethyl acetate, in the presence of an amount of from 0.4 to 0.6 mol of 1-hydroxybenzotriazole per mol of the compound of formula (IV) employed and in the presence of an amount of from 1 to 1.2 mol of dicyclohexylcarbodiimide per mol of compound of formula (IV) employed, in the absence of triethylamine, at a temperature of 20 to 77Â° C., to yield, after isolation, the compound of formula (VI): which is low in the impurities of formulae (VII) and (VIII) in which Bn represents benzyl, and the carboxylic group of the heterocycle of the formula (IV) is deprotected by catalytic hydrogenation to yield perindopril of formula (I), which is low in the impurities of formulae (II) and (III): wherein the perindopril is converted, if desired, into a pharmaceutically acceptable salt.