Preparation of 2-carboxymethylpyrimidines analogous to the pyrimidine of thiamine and some of their pyridine isomers

Abstract

Basic hydrolysis of 4-amino-5-cyano-2-2′-hydroxyethylpyrimidine (IV) yields 4-amino-5-carboxy-2-2′-hydroxyethylpyrimidine (V) and catalytic hydrogenation in aqueous hydrochloric acid yields 4-amino-5-formyl-2-2′-hydroxyethylpyrimidine (VI) which is reduced by sodium borohydride to 4-amino-2-2′-hydroxyethyl-5-hydroxymethylpyrimidine (VII). Attempts to oxidise the alcohol function of (IV) were without success. Condensation of ethoxymethylenemalononitrile with ethoxycarbonylamidine yields 2,6-diamino-3-cyano-5-ethoxycarbonylpyridine (IX) which is hydrolysed to 2,6-diamino-3,5-dicarboxypyridine (X) and catalytically hydrogenated to 2,6-diamino-3-aminomethyl-5-ethoxycarbonylpyridine (XI). The latter compound yields 2,6-diamino-5-carboxy-3-aminomethyl-pyridine (XII) after basic hydrolysis. However condensation of malonamide amidine with ethoxymethylenemalononitrile does yield 2-acetamido-4-amino-5-cyanopyrimidine (XIII) which is easily hydrolysed to the unstable 4-amino-5-carboxy-2-carboxymethylpyrimidine (XIV) and catalytically hydrogenated 2-acetamido-4-amino-5-formylpyrimidine (XVI). The latter is reduced by sodium borohydride to 2-acetamido-4-amino-5-hydroxymethylpyrimidine (XVII) which on basic hydrolysis yields 4-amino-2-carboxymethyl-5-hydroxymethylpyrimidine (I) the carboxymethyl analogue of the pyrimidine of thiamine.