Patent ID: 7666896
Filing Date: 2010-02-23
Classification: A61P,C07K

Abstract:
1. A process for preparing perindopril, or a pharmaceutically acceptable salt thereof, which process comprises: (i) condensation of norvaline ethyl ester with pyruvic acid to yield N—[(S)-1-carbethoxybutyl]-(S)-alanine (II), wherein said condensation is carried out under catalytic hydrogenation at a pressure ranging from 5 to 10 bars and said catalyst and any inorganic salts present in the reaction medium are removed by filtration to obtain a filtrate, the filtrate is concentrated and N—[(S)-1-carbethoxybutyl]-(S)-alanine is isolated by precipitation by the addition of a solvent selected from acetone and ethyl acetate; (ii) conversion of an alkali metal salt of S-indoline-2-carboxylic acid to (2S,3aS,7aS)-octahydroindole-2-carboxylic acid by hydrogenation using 5% rhodium on alumina at a pressure of from 5 to 20 bar; (iii) preparing a substituted benzyl ester of the (2S,3aS,7aS)-octahydroindole-2-carboxylic acid (I), by reaction of (2S,3aS,7aS)-octahydroindole-2-carboxylic acid with the corresponding substituted benzyl alcohol of formula HOCH (iv) coupling the substituted benzyl ester of (2S,3aS,7aS)-octahydroindole-2-carboxylic acid (I) from step (iii) with the N—[(S)-carbethoxybutyl]-(S)-alanine (II) from step (i) to form the ester of formula III, wherein the coupling is carried out in the presence of N,N-dicyclohexyl carbodiimide (DCC) and 1-hydroxybenzotriazole (HOBT); and converting the ester of formula III to perindopril or a pharmaceutically acceptable salt thereof.