Process for the preparation of chymase modulators

Abstract

The present invention is a process for the preparation of chymase modulators, useful in the treatment of inflammatory and serine protease mediated disorders.

We claim: 
     
         1 . A process for the preparation of a compound of formula (III) 
       
         
           
           
               
               
           
         
         comprising the step of 
       
       
         
           
           
               
               
           
         
         (a) reacting a compound of formula (II) with a brominating agent; in the presence of a catalyst; in a mixture of water and an organic solvent; to yield the corresponding compound of formula (III). 
       
     
     
         2 . A process as in  claim 1 , wherein the compound of formula (II) is present in an excess of its corresponding trans isomer; wherein the brominating agent is 1-bromo-pyrrolidine-2,5-dione; wherein the brominating agent is present in an amount of about 1.1 molar equivalents; wherein the catalyst is manganese acetate hydrate; wherein the catalyst is present in an amount of about 0.5 molar equivalents; wherein the organic solvent is acetonitrile; and wherein the compound of formula (II) is reacted with brominating agent at a temperature in the range of from about 25° C. to about 70° C.