Process for making amlodipine, derivatives thereof, and precursors therefor

Abstract

Amlodipine and related analogues thereof are prepared by the following general reaction scheme: R 1 and R 2 each independently represent a C 1 -C 4 alkyl group. The process provides for the formation of compounds of formula (1) in good yield and purity. Further, the compounds of formula (1) can be used as calcium channel blockers or as reference standards or reference markers for checking the purity of amlodipine.

1 . A process, which comprises reacting o-chlorobenzaldehyde with a compound of formula (C):  
       
         
           
           
               
               
           
         
       
       wherein R 2  represents a C 1 -C 4  alkyl group, to form a compound of formula (3):  
       
         
           
           
               
               
           
         
       
       wherein R 2  represents a C 1 -C 4  alkyl group.  
     
     
         2 . The process according to  claim 1 , wherein said reaction is carried out in an organic solvent.  
     
     
         3 . The process according to  claim 2 , wherein said solvent is isopropanol.  
     
     
         4 . The process according to  claim 2 , which further comprises recovering said compound of formula (3) from said solvent.  
     
     
         5 . The process according to  claim 1 , wherein R 2  in formulas (C) and (3) is a methyl, ethyl or isopropyl group.  
     
     
         6 . The process according to  claim 5 , wherein R 2  in formulas (C) and (3) is an ethyl group.  
     
     
         7 . The process according to  claim 6 , wherein said reaction is carried out in an organic solvent.  
     
     
         8 . The process according to  claim 7 , wherein said solvent is isopropanol.  
     
     
         9 . The process according to  claim 8 , which further comprises recovering said compound of formula (3) from said solvent.