Novel method for the synthesis of furo[2,3-d]pyrimidines by cyclization of 4-(phenacyloxy)pyrimidine-5-carbonitriles

Abstract

It is known that alkylation of 4(3H)-pyrimidinones occurs with the formation of a mixture of N(1)-, N(3)-, and O-alkylation products [1, 2]. We have previously found [3, 4] that reaction of 5-cyano-2-methylsulfanyl-4(3H)-pyrimidinone (1) with 4-substituted w-bromoacetophenones 2a,b in the presence of potassium carbonate and a catalytic amount of potassium iodide in anhydrous acetonitrile medium readily gives all three of the O-, N(1)-, and N(3)- alkylations. The main reaction course (O-alkylation) gives the 2-methylsulfanyl-4-(phenacyloxy)pyrimidine-5-carbonitriles 3a,b in preparative yields of 37-50%. In continuing our study of the alkylation of 4(3H)-pyrimidinones we report here a novel synthetic route to the furo[2,3-d]pyrimidine system via cyclization of 2-methylsulfanyl-4-(phenacyloxy)pyrimidine-5-carbonitriles 3a,b. Interest in the method of synthesis of furo[2,3-d]pyrimidines is due to the wide spectrum of biological activity of these compounds [5-8].