| 摘要 |
A process for the preparation of clevudine as anti-HBV(hepatitis B virus) agent is provided to improve preparation yield and purity by inhibiting production of by-products through employment of hydroxyl anion exchange resin in preparation and purification of clevudine, and reduce the reaction time by using alkali metal salt as deprotecting reagent. A process for the preparation of clevudine as anti-HBV agent comprises the steps of: reacting 1,3,5-tri-O-benzoyl-alpha-L-ribofuranoside(HTBR) with sulfuryl chloride and imidazol to prepare 2-O-imidazolylsulfonyl-1,3,5-tri-O-benzoyl-alpha-L-ribofuranoside(ITBR) and purifying ITBR with hydroxyl anion exchange resin at -10 to 40 deg. C; introducing fluorine into ITBR to prepare 2-deoxy-2-fluoro-1,3,5-tri-O-benzoyl-alpha-L-ribofuranoside(FTBR); halogenizing FTBR and subjecting the halogenized FTBR to thymine condensation to prepare 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-beta-1-arabinofuranosyl) thymine(DFAT); and deprotecting DFAT by reacting with alkali metal salt in methanol at 40-80 deg. C. Further, the alkali metal salt is one or more selected from sodium hydrogen carbonate, potassium bicarbonate, sodium carbonate and potassium carbonate.
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