Process for producing v-coelenterazine compounds

Abstract

A simple process for producing ν-coelenterazine compounds has been desired. The invention provides a process for producing a ν-coelenterazine compound represented by general formula (II) which comprises (1) the step of reacting a compound represented by general formula (VIII) with a methyltriphenylphosphonium salt in the presence of a base to give a compound represented by general formula (IX), (2) the step of performing a ring-closing metathesis reaction on any one selected from the group consisting of the compound represented by general formula (IX) and a compound represented by general formula (X) which is the compound represented by general formula (IX) wherein the amino is protected with R 5 , and then deprotecting R 4 and, if any, R 5 to give a ν-coelenteramine compound represented by general formula (XIV), and (3) the step of reacting the compound represented by general formula (XIV) with a compound represented by general formula (XV) to give the compound represented by general formula (II).

1 - 13 . (canceled) 
     
     
         14 . The method for producing a compound represented by formula (VIII): 
       
         
           
           
               
               
           
         
       
       wherein R 1  is hydrogen, a halogen, a substituted or unsubstituted hydrocarbon group, or a substituted or unsubstituted heterocyclic group, and R 4  is a protecting group,
 which comprises: (1) reacting 2-amino-3,5-diburomo-6-chloropyrazine with R 1 MgX and ZnCl 2 , wherein R 1  is the same as defined above and X is a halogen, in the presence of a palladium catalyst to give a compound represented by formula (V): 
 
       
         
           
           
               
               
           
         
       
       wherein R 1  is the same as defined above,
 (2) reacting the compound represented by formula (V) with a compound represented by formula (VI): 
 
       
         
           
           
               
               
           
         
       
       wherein R 4  is the same as defined above, in the presence of a palladium catalyst and a base to give a compound represented by formula (VII): 
       
         
           
           
               
               
           
         
       
       wherein R 1  and R 4  are the same as defined above, and,
 (3) reacting the compound represented by formula (VII) with tributyl(vinyl)tin in the presence of a palladium catalyst to give the compound represented by formula (VIII).