METHOD FOR PRODUCING 3′-AZIDO-2′,3′--DIDESOXYTHYMIDINE Russian patent published in 1998 - IPC

FIELD: organic chemistry; pharmaceutical industry. SUBSTANCE: 3′--azido-2′,3′--didesoxythymidine is prepared by consequent interaction of 1,2-isopropylidene-α-D-xylofuranose with benzoyl chloride and with methane sulfochloride, molar ratio of components is 1:0.7-1.2 and 1:1-2.5, respectively. Product is acylated by acetic anhydride in acetic acid, H₂SO₄ being added; the process takes place at molar ratio 1:3-1:20-50:1-5. Compound is condensed with silylated thymine, the process takes place in the presence of SnCl₄ in acetonitrile solution. Yield of intermediate nucleoside is 90 %. Intermediate product is affected by desacylation which takes place by heating at 75 C in solution of acetonitrile and 1 M aqueous solution of H₂SO₄. Desacylated compound of SOCl₂ is boiled in acetonitrile medium to prepare chloro-derivative of nucleoside at 80 % yield. By treatment with tributyl tin hydride in the presence of AlBN 2-desoxy-derivative is prepared at 90 % yield. By heating thus prepared product at 150 C with NaN₃ in dimethyl formamide and by treatment with excess of MeoNa in methanol product is obtained. Total yield of compound is 25.16 % (as calculated for D-xylose). EFFECT: improved efficiency. 4 tbl