Synthesis of 3-methylisoguanine [6-amino-3-methylpurin-2(3H)-one]

Abstract

The first synthesis of 3-methylisoguanine is reported. Methylation of 4,6-diamino-2-hydroxypyrimidine (I) at pH 11·6 gave the 1-methyl derivative (II), which on nitrosation and reduction yielded 4,5,6-triamino-1-methylpyrimidin-2(1H)-one (IV). Cyclisation either via the 5-formamido-derivative (VII) or directly by use of diethoxymethyl acetate [or, preferably, formic acid–formamide (77% yield)] gave 3-methylisoguanine (V) exclusively. Its structure was established by deamination to 3-methylxanthine, no 1-methylxanthine being obtained.