5-protected aminopyrimidine compound, production method thereof and intermediate therefor

Abstract

The present invention provides a production method of 5-aminopyrimidine compound represented by the formula (5) by reacting a glycine compound represented by the formula (1) with t-butoxybisdimethylaminomethane, dimethylformamidedimethylacetal or dimethylformamidediethylacetal to produce a dialkylaminomethylene compound represented by the formula (2), reacting the compound of formula (2) in the presence of an acid to produce a hydroxymethylene compound represented by the formula (3), and reacting the compound of formula (3) with an amidine compound represented by the formula (4) or a salt thereof.

1 . A hydroxymethylene compound of formula (3-a) or a salt thereof: 
     
       
         
         
             
             
         
       
       wherein R 1  is an alkyl group, p 3  is a hydrogen atom or a benzyl group, p 4  is a urethane type protecting group when p 3  is a hydrogen atom, or a benzyl group when p 3  is a benzyl group, or p 3  and p 4  are linked to show a phthaloyl group, M is a hydrogen atom or an alkali metal. 
     
   
   
       2 . The compound of  claim 1 , wherein R 1  is a methyl group or an ethyl group and M is a hydrogen atom, sodium, potassium or lithium. 
   
   
       3 . The compound of  claim 1 , wherein the compound represented by the formula (3-a) is methyl-2-benzyloxycarbonylamino-3-hydroxymethylene-glycinate or a alkali metal salt thereof. 
   
   
       4 . A 5-protected aminopyrimidine compound of formula (5-a) or a salt thereof: 
     
       
         
         
             
             
         
       
       wherein p 3  is a hydrogen atom or a benzyl group, p 4  is a urethane type protecting group when p 3  is a hydrogen atom, or a benzyl group when p 3  is a benzyl group, or p 3  and p 4  are linked to show a phthaloyl group, and R3 is a group of formula (a) or formula (b):
   —O—R 4  (a) —S—R 4  (b) 
 
       wherein R 4  is an alkyl group optionally having substituents, an aryl group optionally having substituents or an aralkyl group optionally having substituents. 
     
   
   
       5 . The compound of  claim 4 , wherein the compound represented by the formula (5-a) is selected from the group consisting of 2-methoxy-6-oxo-5-benzyloxycarbonylamino-1,6-dihydropyrimidine, 2-S-methyl-6-oxo-5-benzyloxycarbonylamino-1,6-dihydropyrimidine, and 2-phenyl-6-oxo-5-benzyloxycarbonylamino-1,6-dihydropyrimidine.