Process for preparing 3-acylaminobenzofuran-2-carboxylic acid derivative

Abstract

The present invention provides a process of preparing a compound of the formula [I]: wherein X is a group of the formula: —N═ or —CH═; R 1 is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a cyano group or an amino group optionally substituted by a lower alkyl group; Ring A is a nitrogen-containing heterocyclic group; Ring B is an optionally substituted benzene ring or an optionally substituted pyridine ring; and R 3 is a hydrogen atom or a lower alkyl group, or a pharmaceutically acceptable salt thereof, which is useful as an inhibitor of activated blood coagulation factor X.

1 . A process for preparing a compound of the formula [VI′]: 
     
       
         
         
             
             
         
       
     
     wherein Ring C is an optionally substituted aromatic ring and the formula: NR 4 R 5  is an optionally substituted amino group or an optionally substituted nitrogen-containing heterocyclic group, which comprises reacting a compound of the formula [II′]: 
     
       
         
         
             
             
         
       
     
     wherein X 1  is a leaving group and other symbol is the same as defined above with a compound of the formula [III′]: 
     
       
         
         
             
             
         
       
     
     wherein the symbols are the same as defined above in the presence of a group VIII metal compound supported by a solid phase. 
   
   
       2 . A process for preparing a compound of the formula [VII″]: 
     
       
         
         
             
             
         
       
     
     wherein R 01  is a hydrogen atom and the formula: NR 41 R 51  is a substituted amino group or a substituted nitrogen-containing heterocyclic group, which comprises subjecting a compound of the formula [VI″]: 
     
       
         
         
             
             
         
       
     
     wherein the symbols are the same as defined above to catalytic reduction under low pressure and neutral to slightly basic conditions in the presence of a rhodium-carbon catalyst. 
   
   
       3 . A process for preparing a trans-form compound of the formula [VIII′]: 
     
       
         
         
             
             
         
       
     
     wherein R 6  is a substituent, or a carboxylic acid derivative thereof, which comprises isomerizing a cis-form or a mixture of cis- and trans-forms of a carboxylic acid derivative of the formula [VII′]: 
     
       
         
         
             
             
         
       
     
     wherein the symbol is the same as defined above in the presence of a slight amount of water, and also in the presence of an alkali metal alkoxide or an alkali metal amide. 
   
   
       4 . A process for preparing a compound of the formula [X′]: 
     
       
         
         
             
             
         
       
     
     wherein Ring B′ is an optionally substituted aromatic ring, which comprises cyanation of a compound of the formula [IX′]: 
     
       
         
         
             
             
         
       
     
     wherein X 4  is a leaving group and other symbol is the same as defined above in the presence of a group VIII metal compound supported by a solid phase and a phosphine ligand. 
   
   
       5 . A process for preparing a compound of the formula [VII′″]: 
     
       
         
         
             
             
         
       
     
     wherein R 02  is a lower alkyl group and the formula: NR 42 R 52  is a substituted amino group or a substituted nitrogen-containing heterocyclic group, which comprises subjecting a compound of the formula [VI′″]: 
     
       
         
         
             
             
         
       
     
     wherein the symbols are the same as defined above to catalytic reduction under low pressure in the presence of a rhodium-carbon catalyst. 
   
   
       6 . A process for preparing a compound of the formula [VII″″]: 
     
       
         
         
             
             
         
       
     
     wherein R 03  is a lower alkyl group and the formula: NR 43 R 53  is an unsubstituted amino group, which comprises subjecting a compound of the formula [VI″″]: 
     
       
         
         
             
             
         
       
     
     wherein the symbols are the same as defined above to catalytic reduction under low pressure and neutral to slightly basic conditions in the presence of a rhodium-carbon catalyst. 
   
   
       7 . The process according to  claim 1 , wherein the group VIII metal compound is palladium or nickel, and the reaction is carried out in the presence of a ligand. 
   
   
       8 . The process according to  claim 2 , which is carried out under a condition of pH 7-8. 
   
   
       9 . The process according to  claim 8 , wherein the formula: NR 41 R 51  is a substituted amino group or a substituted pyrrolidinyl group. 
   
   
       10 . The process according to  claim 6 , which is carried out under an acidic condition with acetic acid. 
   
   
       11 . The process according to  claim 10 , wherein the formula: NR 43 R 52  is an amino group. 
   
   
       12 . The process according to  claim 4 , wherein the a group VIII metal compound is palladium or nickel, and the reaction is carried out in the presence of a ligand. 
   
   
       13 . The process according to  claim 12 , which is carried out in the presence of palladium-carbon, zinc and bromine. 
   
   
       14 . The process according to  claim 12 , wherein Ring B′ is an optionally substituted benzene ring or an optionally substituted pyridine ring, and X 4  is a halogen atom. 
   
   
       15 . The process according to  claim 4 , wherein the phosphine ligand is triphenylphosphine.