Synthesis of 6-(alkoxymethyl)- and 6-(alkylsulfanylmethyl)furo[2,3-d]pyrimidin-2(3H)-one analogues

Treatment of 6-(hydroxymethyl)furo[2,3-d]pyrimidin-2(3H)-one (2) with 1-iodoalkanes and potassium carbonate resulted in predominant formation of N3 (and minor amounts of O2) alkylated regioisomers. Treatment of the 3-alkyl products (3) with thionyl chloride gave highly reactive 6-chloromethyl intermediates (5). Direct solvolysis of 5 in alcohol solutions (similar to 50 degrees C) produced 3-alkyl-6-(alkoxymethyl)furopyrimidin-2(3H)-ones (6), whereas extensive decomposition of 5 occurred with added base promoters. Sonication of 5 with sodium thioacetate in acetonitrile gave the air-stable 6-(alkylsulfanylmethyl) intermediates (7), which were subjected to deacetylation (methanolic sodium methoxide) and in situ alkylation to give 3-alkyl-6-(alkylsulfanylmethyl)furo[2,3-d]pyrimidin-2(3H)-ones (8). Lipophilic derivatives of furo[2,3-d]pyrimidin-2(3H)-one are of interest as potential inhibitors of viral penetration of cells.