Investigations into the synthesis of 6-ethyl-5-(4-pyridinyl)-2,4-pyrimidinediamine as a potential antimalarial agent

The synthesis of 6-ethyl-5-(4-pyridinyl)-2,4-pyrimidinediamine ( 2 ), the pyridine analog of pyrimethamine, is described. Condensation of 4-pyridineacetonitrile ( 3 ) with methyl propionate afforded α-(1-oxopropyl)-4-pyridineacetonitrile ( 4 ). Treatment with triethyl orthopropionate gave primarily the undesired N-alkylated material. However reaction of the crude mixture with guanidine afforded 2 in low yield. This material was devoid of significant antimalarial activity.