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The synthesis of a pyrido[3,4‐ d ]pyrimidine analog of pteroic acid
Author(s) -
Maguire James H.,
Mckee Robert L.
Publication year - 1979
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570160125
Subject(s) - chemistry , alkaline hydrolysis , pyrimidine , hydrolysis , halogenation , condensation , alkali metal , organic chemistry , stereochemistry , medicinal chemistry , physics , thermodynamics
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(3 H ) 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).