Process for the preparation of perindopril

Abstract

A process for preparing perindopril is provided comprising condensing an N-[(S)-1-carbethoxybutyl]-(S)-alanyl halide of formula II: wherein X is a halide with an (2S,3aS,7aS)-2-carboxyperhydroindole of formula III: wherein R is hydrogen or a protecting group.

1 - 17 . (canceled)  
     
     
         18 . Perindopril erbumine prepared in accordance with a process comprising (a) condensing an N-[(S)-1-carbethoxybutyl]-(S)-alanyl halide of formula II:  
       
         
           
           
               
               
           
         
       
       wherein X is a halide with an (2S,3aS,7aS)-2-carboxyperhydroindole of formula III:  
       
         
           
           
               
               
           
         
       
       wherein R is hydrogen or a protecting group and converting the product of step (a) to perindopril erbumine having a purity of greater than or equal to about 95%.  
     
     
         19 . (canceled)  
     
     
         20 . The perindopril erbumine of  claim 18 , wherein the step of condensing is carried out in one or more organic solvents and in the presence of a base.  
     
     
         21 . The perindopril erbumine of  claim 20 , wherein the organic solvent is one or more anhydrous solvents.  
     
     
         22 . The perindopril erbumine of  claim 21 , wherein the anhydrous solvent is a chlorinated hydrocarbon selected from the group consisting of dichloromethane, dichloroethane and mixtures thereof.  
     
     
         23 . The perindopril erbumine of  claim 21 , wherein the anhydrous solvent is an aromatic hydrocarbon selected from the group consisting of benzene, toluene, and mixtures thereof.  
     
     
         24 . The perindopril erbumine of  claim 21 , wherein the anhydrous solvent is an aliphatic hydrocarbon selected from the group consisting of hexane, heptane, and mixtures thereof.  
     
     
         25 . The perindopril erbumine of  claim 21 , wherein the anhydrous solvent is a cycloaliphatic hydrocarbon selected from the group consisting of cyclopentane, cyclohexane and mixtures thereof.  
     
     
         26 . The perindopril erbumine of  claim 18 , wherein R of Formula III is a protecting group of the formula Si(R 1 )(R 2 )(R 3 ), wherein R 1 , R 2  and R 3  are independently a straight or branched alkyl or aryl group having from 1 to about 25 carbon atoms.  
     
     
         27 . The perindopril erbumine of  claim 18 , wherein step (b) comprises treating perindopril with tert-butylamine to provide perindopril erbumine.  
     
     
         28 . The perindopril erbumine of  claim 18 , having purity greater than 99.5%.