公开(公告)号：US20230348390A1

公开(公告)日：2023-11-02

申请号：US18000111

申请日：2021-05-26

申请人： Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.

发明人： Haiwen HU ,  Hongliang FU ,  Fenfen CHEN ,  Xinjie ZHOU

IPC分类号： C07D213/55

CPC分类号： C07D213/55

摘要： The invention provides a method for preparing a key intermediate for the synthesis of (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)propionic acid dihydrochloride: methyl (S)-2-amino-3-(4-(2,3-dimethylpyridin-4-yl)phenylpropionate and the salt thereof. The method adopts continuous feeding mode, does not require column chromatographic purification, simplifies the procedures, reduces loss and increases yield. Furthermore, the product, i.e., salt of methyl (S)-2-amino-3-(4-(2,3-dimethylpyridin-4-yl)phenylpropionate, obtained by the purification mode of salt formation, has high purity and good storage stability. The preparation method of the invention can achieve a total yield of above 85%, a purity of the target product of above 98%, and a content of the isomer of below 0.5%. In addition, the method of the invention has good process stability, can produce quality-controlled product, and can be applied to industrial production.

公开(公告)号：US20230174547A1

公开(公告)日：2023-06-08

申请号：US17995091

申请日：2021-03-02

申请人： Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.

发明人： Haiwen HU ,  Li FANG ,  Fan HU ,  Xinjie ZHOU ,  Fenfen CHEN

IPC分类号： C07D491/056

CPC分类号： C07D491/056 ,  C07B2200/13

摘要： The invention provides pharmaceutically acceptable acid salts of (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl) propionic acid (“OAD2”) and the preparation method thereof. The pharmaceutically acceptable acid salts of OAD2 provided herein may be useful in the treatment of various conditions and metabolic disorders including, but not limited to, type 2 diabetes.

公开(公告)号：US20230174546A1

公开(公告)日：2023-06-08

申请号：US17995090

申请日：2021-03-02

申请人： Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.

发明人： Haiwen HU ,  Li FANG ,  Fan HU ,  Fenfen CHEN ,  Xinjie ZHOU

IPC分类号： C07D491/056

CPC分类号： C07D491/056 ,  C07B2200/13

摘要： The invention relates to a crystal form A of (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl) -2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)propionic acid (“OAD2”) , and methods of preparation thereof. Crystal form A may be useful in the treatment of various conditions and metabolic disorders including, but not limited to, type 2 diabetes.