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

The synthesis of two metabolites M3 and M4 of 2,4‐diamino‐5‐(3, 4, 5‐trimethoxybenzyl)‐pyrimidine (trimethoprim, 1) is reported. M3 (trimethoprim 1‐oxide) as well as the isomeric 3‐oxide were prepared by oxidation of 1 with m‐chloroperbenzoic acid. The structure of M3 was finally established by x‐ra analysis [4]. The metabolite M4 [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.