Process for the Synthesis of a CPLA2 Inhibitor

Abstract

A process for making a substituted indole compound, including the steps of: reacting the compounds in a non-protic polar solvent in the presence of a catalyst to form the intermediate compound wherein Ph and X are as defined herein; and then, heating this intermediate compound in the solvent in the presence of the catalyst to form the substituted indole compound The invention also includes compounds formed by this process.

1 - 12 . (canceled) 
     
     
         13 . A process for making the compound 
       
         
           
           
               
               
           
         
       
       comprising the reaction step 
       
         
           
           
               
               
           
         
       
       wherein Ar represents phenyl optionally substituted with one to three halogen atoms;
 R represents C 1 -C 6 -alkyl, phenyl, —CH 2 O-phenyl, —CH 2 O-(C 1 -C 6 -alkyl), —CH 2 -phenyl, —CH 2 CH 2 -phenyl, or —CH 2 -phenyl—COOZ; 
 Z represents H or C 1 -C 6 -alkyl; 
 Ph represents phenyl; and 
 X represents a moiety selected from the group consisting of H, F, Cl, Br, C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, and C 6 -C 10 -aryl, the alkyl moiety being optionally substituted with one or more atoms selected from F, Cl and Br, and the cycloalkyl and aryl moieties being optionally substituted with from one to three substituents selected from F, Cl, Br and C 1 -C 6 -alkyl. 
 
     
     
         14 . The process of  claim 13  wherein X is F, Cl or Br; R is —CH 2 -phenyl, —CH 2 CH 2 -phenyl, or —CH 2 -phenyl—COOZ; and Z is H or C 1 -C 6 -alkyl. 
     
     
         15 . The process of  claim 14  wherein X is Cl, R is —CH 2 -phenyl—COOH, and Ar is 3,4-dichlorophenyl. 
     
     
         16 . A process for making the compound 
       
         
           
           
               
               
           
         
       
       comprising the step of reacting the compound 
       
         
           
           
               
               
           
         
       
       in N,N-dimethylformamide in the presence of copper iodide to form the substituted indole compound 
       
         
           
           
               
               
           
         
         wherein Ar represents phenyl optionally substituted with one to three halogen atoms; 
         R represents C 1 -C 6 -alkyl, phenyl, —CH 2 O-phenyl, —CH 2 O-(C 1 -C 6 -alkyl), —CH 2 -phenyl, —CH 2 CH 2 -phenyl, or —CH 2 -phenyl—COOZ; 
         Z represents H or C 1 -C 6 -alkyl; 
         Ph represents phenyl; and 
         X represents a moiety selected from the group consisting of H, F, Cl, Br, C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, and C 6 -C 10 -aryl, the alkyl moiety being optionally substituted with one or more atoms selected from F, Cl and Br, and the cycloalkyl and aryl moieties being optionally substituted with from one to three substituents selected from F, Cl, Br and C 1 -C 6 -alkyl. 
       
     
     
         17 . The process of  claim 16  wherein X is F, Cl or Br; R is —CH 2 -phenyl, —CH 2 CH 2 -phenyl, or —CH 2 -phenyl—COOZ; and Z is H or C 1 -C 6 -alkyl. 
     
     
         18 . The process of  claim 17  wherein X is Cl, R is —CH 2 -phenyl—COOH, and Ar is 3,4-dichlorophenyl. 
     
     
         19 . A process for making the compound 
       
         
           
           
               
               
           
         
       
       comprising the reaction steps 
       
         
           
           
               
               
           
         
       
     
     
         20 - 22 . (canceled)