SYNTHESIS OF A PYRIDO[3,4-D]PYRIMIDINE ANALOG OF PTEROIC ACID

A multistep synthesis of ethyl 5‐amino‐2‐methyIpyridine‐4‐carboxylate (5a) starting from ethyl acetopyruvate and nitroacetamide is described. The condensation of 5a with benzoylcyanamide gave 2‐amino‐3‐benzoyl‐6‐methylpyrido[3,4‐d]pyrimidin‐4(3H) one (10), which could be hydrolyzed in alkali to give 2‐amino‐4‐hydroxy‐6‐methylpyrido[3,4‐d]pyrimidine (9). Free radical bromination of 10 in bromotrichloromethane gave a mixture of the bromo‐ and chloromethyl‐ derivatives (11). Fusion of 11 with ethyl p‐aminobenzoate, followed by alkaline hydrolysis gave the corresponding pteroic acid analog (12). Copyright © 1979 Journal of Heterocyclic Chemistry