Process for producing heterocyclic compound

Abstract

The present invention provides a method of efficiently producing an optically active 6-(3-aminopiperidin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine derivative. The optically active piperidine-3-carboxamide or a derivative thereof, which is obtained by subjecting 1,4,5,6-tetrahydropyridine-3-carboxamide or a derivative thereof to an asymmetric reduction in the presence of a catalyst, is used as an intermediate.

1 . A method of producing an optically active form of a compound represented by the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or a protecting group; 
         R 2 , R 3  and R 4  are independently a hydrogen atom or a substituent; 
         R 5  and R 6  are independently a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocyclic group; or 
         R 1  and R 2  in combination, R 2  and R 3  in combination, R 3  and R 4  in combination, or R 5  and R 6  in combination optionally form a 5- to 8-membered ring together with the adjacent atoms, and the carbon atom marked with * is an asymmetric carbon atom, or a salt thereof, which comprises subjecting a compound represented by the formula: 
       
       
         
           
           
               
               
           
         
         wherein each symbol is as defined above, 
         or a salt thereof, to a hydrogenation reaction in the presence of an organic metal complex. 
       
     
     
         2 . The method according to  claim 1 , wherein the organic metal complex is a transition metal complex. 
     
     
         3 . The method according to  claim 2 , wherein the transition metal complex is a ruthenium complex. 
     
     
         4 . The method according to  claim 3 , wherein the ruthenium complex is represented by the formula:
   [Ru(OCOR a ) 2 L*]  (VIII)
   wherein   R a  is an optionally substituted C 1-3  alkyl group; and   L a  is a diphosphine ligand.   
     
     
         5 . The method according to  claim 1 , wherein the hydrogenation reaction is performed in the presence of an alkali metal halide or a compound represented by the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R A , R B , R C  and R D  are independently a hydrogen atom, or an optionally substituted hydrocarbon group; and 
         X is a halogen atom. 
       
     
     
         6 . A compound represented by the formula: 
       
         
           
           
               
               
           
         
         wherein R is an optionally substituted hydrocarbon group. 
       
     
     
         7 . An optically active form of a compound represented by the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R is an optionally substituted hydrocarbon group, and 
         the carbon atom marked with * is an asymmetric carbon atom.