Unusual dihydrazone formation in the Fischer-indole cyclization. The synthesis of novel nonclassical annulated 2,4-diaminopyrrolo[2,3-d]pyrimidine antifolates

The synthesis of seven novel tetracyclic 2,4-diaminopyrrolo[2,3-d]pyrimidin es as conformationally restricted nonclassical antifolates was achieved via an unusual Fischer-indole cyclization of dihydrazones. An attempted synthe sis of 2,4-diamino-6-hydrazinopyrimidine afforded 2-amino-4,6-dihydrazinopy rimidine which when reacted with appropriate ketones gave the dihydrazones. The dihydrazones in turn under Fischer-indole cyclization conditions affor ded target conformationally restricted tetracyclic products.