New syntheses of 7-substituted-2-aminothieno- and furo[3,2-d]pyrimidines

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In a recent publication, we have the described the synthesis of 7-substituted-2-amino-1,5-dihydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones which are potent inhibitors of the enzyme Purine Nucleoside Phosphorylase from the corresponding 3-aminopyrroIe-2-carboxylate esters. A key step in the synthesis is condensation of the amino group with the highly reactive guanylating reagents 3 or 4 followed by annulation. The furo[3,2-d]pyrimidin-4-one and thieno[3,2-d]pyridin-4-one are closely related rings systems. However, these rings have not been reported in the literature with a 2-amino, substituent which would arise from such guanylation reactions. In this report, the syntheses of the novel furans 5 are described based on our improved pyrrole synthesis (Scheme 1). The syntheses of the novel thiophenes 6 are described. The guanylation of 5 and 6 were studied and compared to 2. The 3-amino group of 5 and 6 failed to react with 3 or 4 under mild acid catalysis; conditions under which 2 easily condensed. Guanylation was finally achieved by generating the carbodiimide intermediate of 3 under mercury catalysis affording the guanylated adducts which were converted to the novel 2-aminothieno- and furo[3,2-d]pyrimidin-4-ones 16.