Process for the preparation of lomitapide

Abstract

The present invention relates to a process for preparing Lomitapide or its pharmaceutically acceptable salt thereof having high purity with acceptable levels of impurities.

1 - 10 . (canceled) 
     
     
         11 . The process for the preparation of salt of piperidinyl biphenyl carboxamide derivative of compound of formula III, 
       
         
           
           
               
               
           
         
       
       wherein X represents an acid salt. 
       which comprises:
 i) condensing 4′-(trifluoromethyl)-[1,1′-biphenyl]-2-carboxylic acid of Formula VIII 
 
       
         
           
           
               
               
           
         
          with 4-amino-1-benzyl piperidine of Formula IX 
       
       
         
           
           
               
               
           
         
          to yield benzylpiperidine biphenyl carboxamide derivative of Formula X; 
       
       
         
           
           
               
               
           
         
         ii) optionally isolating the compound of Formula X; 
         iii) optionally purifying the compound of Formula X; 
         iv) converting the compound of Formula X to the acid salt of piperidinyl biphenyl carboxamide derivative of formula III. 
       
     
     
         12 . The process as claimed in  claim 11 , wherein solvent used in step i) selected from the group comprising of methanol, ethanol, isopropanol, methylene chloride, dimethyl formamide, ethyl acetate, isopropyl acetate, acetonitrile, heptane, toluene, n-heptane, n-hexane, diisopropyl ether, tetrahydrofuran, 1,4-dioxane or mixture thereof. 
     
     
         13 . The process as claimed in  claim 11 , wherein debenzylation in step iv) carried out using a metal catalyst is selected from the group comprising of palladium and platinum. 
     
     
         14 . The process as claimed in  claim 11 , wherein acid used in step iv) selected from the group comprising of hydrochloric acid, hydrobromic acid, acetic acid and formic acid. 
     
     
         15 . The process as claimed in  claim 11 , wherein acid salt of compound of Formula III is selected from the group comprising of hydrochloric acid salt, hydrobromic acid salt, acetic acid salt and formic acid salt. 
     
     
         16 - 17 . (canceled) 
     
     
         18 . The process as claimed in  claim 11 , wherein solvent used in step i) selected from the group comprising of methanol, ethanol, methylene chloride, acetonitrile, acetone, ethylacetate, dimethyl formamide or mixture thereof. 
     
     
         19 . The process as claimed in  claim 11 , wherein solvent used in step ii) selected from the group comprising of methanol, ethanol, methylene chloride, acetonitrile, acetone, ethyl acetate, n-heptane, n-hexane, toluene, dimethyl formamide or mixture thereof. 
     
     
         20 . The process as claimed in  claim 11 , wherein acid used in step iii) selected from the group comprising of methane sulfonic acid, acetic acid, formic acid, oxalic acid, hydrochloric acid, hydro bromic acid. 
     
     
         21 . The process as claimed in  claim 11 , wherein solvent used in step iii) selected from the group comprising of methanol, ethanol, isopropyl alcohol, methylene chloride, acetonitrile, acetone, ethyl acetate, n-heptane, n-hexane, toluene or mixture thereof. 
     
     
         22 . The process as claimed in  claim 11 , wherein solvent used in step iv) selected from the group comprising of methanol, ethanol, isopropyl alcohol, methylene chloride, acetonitrile, acetone, ethyl acetate, n-heptane, n-hexane, toluene or mixture thereof.