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    • 92. 发明申请
    • METHOD FOR PRODUCING GEMCITABINE HYDROCHLORIDE AND INTERMEDIATE PRODUCTS
    • 用于生产吉西他滨HYDROCHORID和中间产品
    • WO2009135455A3
    • 2010-01-07
    • PCT/DE2009000499
    • 2009-04-08
    • VORBRUEGGEN HELMUT
    • VORBRUEGGEN HELMUT
    • C07H19/073C07D239/47
    • C07D239/47C07H19/073C07H23/00Y02P20/55
    • The invention relates to methods for producing gemcitabine derivatives of the general formula 6, or gemcitabine hydrochloride 7 (2'-desoxy-2',2'-difluorocytidine hydrochloride), to the silylated cytosine analogs 4c and 4d as intermediate products, and to the use thereof for reactions with 3,5-protected sugars of the general formula 5 into the corresponding protected 2'-desoxycytidines. The subsequent saponification of the protected cytidines removes not only the 3',5'-O-benzoate protecting groups, but also the N4-amidyl group, or the N4-guanidyl group, thereby obtaining the desired free cytidines 6. The subsequent treatment of gemcitabine derivatives of the general formula 6 with acids results in 2'-desoxy-2',2'-difluorocytidine hydrochloride (gemcitabine hydrochloride) 7.
    • 本发明涉及一种用于通式6或Gencitabin盐酸吉西他滨的制备方法7(2'-脱氧-2”,2'- difluorocytidin盐酸盐),甲硅烷基化的胞嘧啶类似物4c和4d作为中间体,以及它们的使用 与通式5的3,5-保护的糖反应,得到相应的保护的2'- deoxycytidines。 受保护的胞苷的随后的水解不仅除去3”,5'-O-苯甲酸酯保护基团,而且该N4-酰胺基团或其中获得所需自由胞苷的N4-胍基。6 通式6与酸的吉西他滨的后续处理导致2'-脱氧-2”,2'- difluorocytidin盐酸盐(盐酸吉西他滨)。7