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Analogs of tetrahydrofolic acid. XXI. Synthesis of 6‐bromomethyl‐5‐( p ‐chlorophenyl)‐2,4‐diaminopyrimidine and its evaluation as a dihydrofolic reductase inhibitor
Author(s) -
Baker B. R.,
Jordaan Johannes H.
Publication year - 1965
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.5570020105
Subject(s) - chemistry , bromide , reductase , pyrimidine , potassium bromide , ether , guanidine , medicinal chemistry , enzyme , stereochemistry , organic chemistry
Abstract The title compound (IV) has been synthesized from p ‐chlorophenylacetonitrile by Claisen condensation with ethyl ethoxyacetate, conversion to an enol ether, then reaction with guanidine to give the key intermediate 5‐( p ‐chlorophenyl)‐2,4‐diamino‐6‐ethoxymethyl‐pyrimidine (V). Cleavage of the ethyl ether of V with hydrogen bromide in acetic acid gave IV. The bromomethylpyrimidine (IV) was a good reversible inhibitor of dihydrofolic reductase from pigeon liver, but IV was not an irreversible inhibitor of the enzyme.