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New syntheses of 7‐substituted‐2‐aminothieno‐ and furo[3,2‐ d ]pyrimidines
Author(s) -
Morris Philip E.,
Elliott Arthur J.,
Montgomery John A.
Publication year - 1999
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570360214
Subject(s) - chemistry , carbodiimide , annulation , stereochemistry , catalysis , synthon , pyrrole , purine nucleoside phosphorylase , adduct , substituent , nucleoside , reagent , amino acid , combinatorial chemistry , purine , organic chemistry , enzyme , biochemistry
In a recent publication, we have the described the synthesis of 7‐substituted‐2‐amino‐1,5‐dihydro‐4 H ‐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.