Synthesis of a pyrrolo annulated pyrido[2,3-D]pyrimidine as a potential nonclassical antifolate

Cyclocondensation of 2,4,6-triaminopyrimidine ( 4 ) with ethyl N-benzyl-4-oxo-3-pyrrolidine carboxylate ( 5 ) in diphenyl ether regiospecifically afforded a new tricyclic, angular 1,3,8-trisubstituted pyrrolo[3′,4′:4,5]-pyrido[2,3-d]pyrimidine-6-one 1 in excellent yield. The ketoester 5 was prepared by a literature method. Compound 1 in addition to being a new heterocyclic system is an important key precursor to a variety of classical and nonclassical tricyclic, 5-deaza analogues of the folate cofactor 5,10-methylenetetrahydrofolate 3 .