公开(公告)号：US10829475B2

公开(公告)日：2020-11-10

申请号：US16795275

申请日：2020-02-19

申请人： KAKEN PHARMACEUTICAL CO., LTD.

发明人： Masahito Watanabe ,  Takeshi Kanayama

IPC分类号： C07D401/06 ,  C07D487/10 ,  C07D401/14 ,  A61P31/10 ,  A61K31/4439

摘要： The present invention provides efinaconazole producing and purifying methods adapted to industrial scale that provide high-purity efinaconazole in high yield by simple operations using specific impurities as indices. The efinaconazole producing method comprises:step A of forming a toluene solution comprising compound (II), compound (III), an inorganic base, and toluene in a volume (L) which is 2 to 5 times the mass (kg) of compound (II);step B of subjecting the toluene solution to reaction under heating;step C of washing the reaction mixture from step B to obtain a toluene solution of crude efinaconazole in which the residual amount of 4-MP is not more than 5 wt % of efinaconazole.

公开(公告)号：US11566000B2

公开(公告)日：2023-01-31

申请号：US17105376

申请日：2020-11-25

申请人： Kaken Pharmaceutical Co. LTD. ,  Botanix SB, Inc.

发明人： Kazuyoshi Marubayashi ,  Masahito Watanabe ,  Herbert R. Brinkman

IPC分类号： C07D207/12 ,  A61K9/00 ,  C07C59/147

摘要： A cocrystal containing the 1′R-diastereomer and the 1'S-diastereomer of sofpironium bromide at a ratio of 1:3 (Form CO), a crystal mixture (for example, Form B) containing Form CO and a crystalline form of the 1′R-diastereomer (Form MN), and a method for preparing sofpironium bromide, which is suitable for manufacture of the crystal mixture are provided. Form CO and a crystalline form of sofpironium bromide containing Form CO (for example, Form B) have superior stability without hygroscopic property, and accordingly they can be preferably used as a raw material of medicaments.

公开(公告)号：US11584715B2

公开(公告)日：2023-02-21

申请号：US17364445

申请日：2021-06-30

申请人： Kaken Pharmaceutical Co. LTD. ,  Botanix SB, Inc.

发明人： Kazuyoshi Marubayashi ,  Masahito Watanabe ,  Herbert R. Brinkman

IPC分类号： C07D207/12 ,  A61K9/00 ,  C07C59/147

摘要： A cocrystal containing the 1′R-diastereomer and the 1′S-diastereomer of sofpironium bromide at a ratio of 1:3 (Form CO), a crystal mixture (for example, Form B) containing Form CO and a crystalline form of the 1′R-diastereomer (Form MN), and a method for preparing sofpironium bromide, which is suitable for manufacture of the crystal mixture are provided. Form CO and a crystalline form of sofpironium bromide containing Form CO (for example, Form B) have superior stability without hygroscopic property, and accordingly they can be preferably used as a raw material of medicaments.