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.

6-bromomethyl-5-(p-chlorophenyl)-2,4-diaminopyrimidine is a promising reversible inhibitor of dihydrofolic reductase from pigeon liver, but not an irreversible inhibitor.

Journal of Heterocyclic Chemistry

Analogs of tetrahydrofolic acid. XXI. Synthesis of 6-bromomethyl-5-(p-chlorophenyl)-2,4-diaminopyrimidine and its evaluation as a dihydrofolic reductase inhibitor†‡

Paper

Analogs of tetrahydrofolic acid. XXI. Synthesis of 6-bromomethyl-5-(p-chlorophenyl)-2,4-diaminopyrimidine and its evaluation as a dihydrofolic reductase inhibitor†‡

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