Synthesis of l-(alkoxymethyl)-5-benzyl-6-methyluracil as potential nonnucleoside HIV-1 RT inhibitors

Article abstract of DOI:10.1080/00397910600772850

1,3-Dibenzyl-6-methyl-5-zincbromomethyluracil 6 was prepared starting from 6-methyluracil 1. The cross-coupling reaction of benzylic zinc reagent 6 with PhI using bis(dibenzylideneacetone) palladium(0) and (o-furyl)3P as catalyst gave 1,3,5-tribenzyl-6-methyluracil 7. The N-1,N-3-dibenzyl group could be removed in dealkylation to give the 5-benzyl-6-methyluracil 8. It was N-1-alkylated with chloromethyl ethyl ether or chloromethyl benzyl ether to obtained the targets 9a and b. All synthesized compounds were tested for their inhibition of HIV-1 reverse transcriptase, and moderate activity were found for target compounds 9a and b and 5. Copyright Taylor & Francis Group, LLC.