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    • 14. 发明申请
    • SEMI-SYNTHESIS PROCEDURES
    • 半合成程序
    • WO2016065290A1
    • 2016-04-28
    • PCT/US2015/057167
    • 2015-10-23
    • TETRAPHASE PHARMACEUTICALS, INC.
    • ZHANG, Wu-YanLAFRANCE, DannyRONN, Magnus, P.
    • C07D207/06C07C231/12C07C245/20C07C237/26
    • C07D295/15C07C231/12C07C237/26C07C245/20C07C2603/46C07D207/06
    • Provided herein are improved processes tor convening C7-amino-substituted tetracyclines to C7-fluoro-substituted tetracyclines, as well as intermediates produced by or used in these processes. In one embodiment, a thermal fluorination method is provided in which a suspension comprising a non-polar organic solvent and a C7-diazo-substituted tetracycline hexafluorophosphate, hexafluoarsenate or hexafluorosilicate salt, or a salt, solvate or combination thereof, is healed to provide a C7-fluoro-substituted tetracycline, or salt, solvate or combination thereof. In another embodiment, a photolytic fluorination is provided in which a solution comprising an ionic liquid and a C-7diazo-substituted tetracycline tetrafluoroborate, hexafluorophosphate, hexafluoroarsenate or hexafluorosilicate salt, or a salt, solvate or combination thereof, is irradiated to provide a C7-fluoro-substituted tetracycline, or salt, solvate or combination thereof.
    • 本文提供了将C7-氨基取代的四环素转化为C7-氟取代的四环素的改进方法,以及由这些方法制备或用于其中的中间体。 在一个实施方案中,提供了一种热氟化方法,其中包含非极性有机溶剂和C7-重氮取代的四环素六氟磷酸盐,六氟代砷酸盐或六氟硅酸盐或其盐,溶剂合物或其组合的悬浮液被愈合以提供 C7-氟取代的四环素,或其盐,溶剂合物或其组合。 在另一个实施方案中,提供光解氟化,其中照射包含离子液体和C-7重氮取代的四氟环四氟硼酸盐,六氟磷酸盐,六氟砷酸盐或六氟硅酸盐或其盐,溶剂合物或其组合的溶液,以提供C7- 氟取代的四环素或其盐,溶剂合物或其组合。