Synthese von zwei Metaboliten des 2,4‐Diamino‐5‐(3,4,5‐tri‐methoxybenzyl)‐pyrimidins (Trimethoprim)

The synthesis of two metabolites M 3 and M 4 of 2,4‐diamino‐5‐(3, 4, 5‐trimethoxybenzyl)‐pyrimidine (trimethoprim, 1 ) is reported. M 3 (trimethoprim 1‐oxide) as well as the isomeric 3‐oxide were prepared by oxidation of 1 with m ‐chloroperbenzoic acid. The structure of M 3 was finally established by x ‐ra analysis [4]. The metabolite M 4 [2, 4‐diamino‐5‐(3‐hydroxy‐4, 5‐dimethoxy‐benzyl)‐pyrimidine] was prepared by condensation of 3‐benzyloxy‐4, 5‐dimethoxybenzaldehyde ( 2 ) with 3‐methoxypropionitrile ( 3 ) and guanidine followed by hydrogenolysis of the intermediate 3‐benzyloxy compound 4 .