Synthesis of 5-dialkylaminomethyl-3′-azido and 3′-fluoro-2′,3′-dideoxyuridines for evaluation as anti-HIV agents

Uracil (8) was substituted in a Mannich reaction to give the 5-substituted dialkylamino-methyluracils11a–f in 65–85% yield. Compounds11a–f were silylated with hexamethyldisilazane and coupled with 2,3-dideoxy-3-fluoro-D-erythro-pentofuranoside4 and 3-azido-2,3-dideoxy-D-erythro-pentofuranoside7 to give the corresponding 3′-fluoro-2′,3′-dideoxynucleosides13a–f and 3′-azido-2′,3′-dideoxy nucleosides16d, f, respectively, by using trimethylsilyl trifluoromethanesulfonate as a catalyst. Deprotection of the 5-O-(4-phenylbenzoyl) protected nucleosides13a–f and16d, f with saturated methanolic ammonia and separation by chromatography yielded the new derivatives of 2′,3′-dideoxy-3′-fluorouridines14a–f and15a–f and 2′,3′-dideoxy-3′-azidouridines17d, f and18d, f.