公开(公告)号：US10087157B2

公开(公告)日：2018-10-02

申请号：US15521162

申请日：2015-10-23

申请人： Tetraphase Pharmaceuticals, Inc.

发明人： Wu-Yan Zhang ,  Danny LaFrance ,  Magnus P. Ronn

IPC分类号： C07D295/15 ,  C07C231/12 ,  C07C245/20 ,  C07C237/26

摘要： Provided herein are improved processes for convening C7-amino-substituted tetracylines 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 tetracyline, 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 tetracyline tetrafluoroborate, hexafluorophosphate, hexafluoroarsenate or hexafluorosilicate salt, or a salt, solvate or combination thereof, is irradiated to provide a C7-fluoro-substituted tetracyline, or salt, solvate or combination thereof.

公开(公告)号：US20190210988A1

公开(公告)日：2019-07-11

申请号：US16059857

申请日：2018-08-09

申请人： Tetraphase Pharmaceuticals, Inc.

发明人： Wu-Yan Zhang ,  Danny LaFrance ,  Magnus P. Ronn

IPC分类号： C07D295/15 ,  C07C237/26 ,  C07C245/20 ,  C07C231/12 ,  C07D207/06

CPC分类号： C07D295/15 ,  C07C231/12 ,  C07C237/26 ,  C07C245/20 ,  C07C2603/46 ,  C07D207/06

摘要： Provided herein are improved processes for converting 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, hexafluoroarsenate or hexafluorosilicate salt, or a salt, solvate or combination thereof, is heated 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 C7-diazo-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.

公开(公告)号：US20170334872A1

公开(公告)日：2017-11-23

申请号：US15521162

申请日：2015-10-23

申请人： Tetraphase Pharmaceuticals, Inc.

发明人： Wu-Yan Zhang ,  Danny LaFrance ,  Magnus P. Ronn

IPC分类号： C07D295/15 ,  C07C231/12 ,  C07C245/20 ,  C07C237/26 ,  C07C2603/46

CPC分类号： C07D295/15 ,  C07C231/12 ,  C07C237/26 ,  C07C245/20 ,  C07C2603/46 ,  C07D207/06

摘要： Provided herein are improved processes for convening C7-amino-substituted tetracylines 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 tetracyline, 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 tetracyline tetrafluoroborate, hexafluorophosphate, hexafluoroarsenate or hexafluorosilicate salt, or a salt, solvate or combination thereof is irradiated to provide a C7-fluoro-substituted tetracyline, or salt, solvate or combination thereof.

公开(公告)号：US11578044B2

公开(公告)日：2023-02-14

申请号：US17188063

申请日：2021-03-01

申请人： Tetraphase Pharmaceuticals, Inc.

发明人： Danny LaFrance ,  Philip C. Hogan ,  Yansheng Liu ,  Minsheng He ,  Chi-Li Chen ,  John Niu

IPC分类号： A61P31/04 ,  C07D295/15 ,  C07D207/06

摘要： The invention relates to crystalline forms of the bis-HCl salt of a compound represented by Structural Formula 1, and pharmaceutical compositions comprising crystalline forms of the bis-HCL salt of a compound represented by Structural Formula 1 described herein. The crystalline forms of the bis-HCl salt of a compound of Structural Formula 1 and compositions comprising the crystalline forms of the compound of Structural Formula 1 provided herein, in particular, crystalline Form I, crystalline Form J, crystalline Form A, and crystalline Form B, or mixtures thereof, can be incorporated into pharmaceutical compositions, which can be used to treat various disorders. Also described herein are methods for preparing the crystalline forms (e.g., Forms I, J, B and A) of the bis-HCl salt of a compound represented by Structural Formula 1.

公开(公告)号：US10961190B2

公开(公告)日：2021-03-30

申请号：US16342779

申请日：2017-10-19

申请人： Tetraphase Pharmaceuticals, Inc.

发明人： Danny LaFrance ,  Philip C. Hogan ,  Yansheng Liu ,  Minsheng He ,  Chi-Li Chen ,  John Niu

IPC分类号： A61P31/04 ,  C07D295/15 ,  C07D207/06

摘要： The invention relates to crystalline forms of the bis-HCI salt of a compound represented by Structural Formula 1, and pharmaceutical compositions comprising crystalline forms of the bis-HCL salt of a compound represented by Structural Formula 1 described herein. The crystalline forms of the bis-HCl salt of a compound of Structural Formula 1 and compositions comprising the crystalline forms of the compound of Structural Formula 1 provided herein, in particular, crystalline Form I, crystalline Form J, crystalline Form A, and crystalline Form B, or mixtures thereof, can be incorporated into pharmaceutical compositions, which can be used to treat various disorders. Also described herein are methods for preparing the crystalline forms (e.g., Forms I, J, B and A) of the bis-HCI salt of a compound represented by Structural Formula 1.

公开(公告)号：US20190256462A1

公开(公告)日：2019-08-22

申请号：US16342779

申请日：2017-10-19

申请人： Tetraphase Pharmaceuticals, Inc.

发明人： Danny LaFrance ,  Philip C. Hogan ,  Yansheng Liu ,  Minsheng He ,  Chi-Li Chen ,  John Niu

IPC分类号： C07D207/06 ,  A61P31/04

摘要： The invention relates to crystalline forms of the bis-HCI salt of a compound represented by Structural Formula 1, and pharmaceutical compositions comprising crystalline forms of the bis-HCL salt of a compound represented by Structural Formula 1 described herein. The crystalline forms of the bis-HCl salt of a compound of Structural Formula 1 and compositions comprising the crystalline forms of the compound of Structural Formula 1 provided herein, in particular, crystalline Form I, crystalline Form J, crystalline Form A, and crystalline Form B, or mixtures thereof, can be incorporated into pharmaceutical compositions, which can be used to treat various disorders. Also described herein are methods for preparing the crystalline forms (e.g., Forms I, J, B and A) of the bis-HCI salt of a compound represented by Structural Formula 1.