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9 条记录 (耗时 0.015 秒)

    METHOD FOR PREPARING METHYL(S)-2-AMINO-3-(4-(2,3-DIMETHYLPYRIDIN-4-YL)PHENYLPROPIONATE AND SALT THEREOF
    1.
    发明公开
    METHOD FOR PREPARING METHYL(S)-2-AMINO-3-(4-(2,3-DIMETHYLPYRIDIN-4-YL)PHENYLPROPIONATE AND SALT THEREOF 审中-公开

    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.

    METHOD FOR PREPARING GLP-1 RECEPTOR AGONIST FREE BASE
    5.
    发明公开
    METHOD FOR PREPARING GLP-1 RECEPTOR AGONIST FREE BASE 审中-公开

    公开(公告)号：US20230348484A1

    公开(公告)日：2023-11-02

    申请号：US18000108

    申请日：2021-05-26

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

    发明人： Haiwen HU ,  Hongliang FU ,  Fenfen CHEN

    IPC分类号： C07D491/056

    CPC分类号： C07D491/056

    摘要： The invention relates the preparation method of a free base GLP-1 receptor agonist, specifically relates to preparation 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 free base. First, compound III is reacted with a condensation agent to give an active ester, and the amino organic acid salt is dissociated in situ and then directly involved in the amide condensation. Subsequently, in the hydrolysis, by means of the workup mode of acid-base neutralization, (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 free base is precipitated from suitable solvent in high purity. The method comprising two steps achieves a yield above 80%, and the purity 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 free base is above 98%. Moreover, the method can achieve large-scale preparation and is suitable for industrial production.

    METHOD FOR PREPARING GLP-1 RECEPTOR AGONIST
    7.
    发明公开
    METHOD FOR PREPARING GLP-1 RECEPTOR AGONIST 审中-公开

    公开(公告)号：US20230348412A1

    公开(公告)日：2023-11-02

    申请号：US18000099

    申请日：2021-05-26

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

    发明人： Fan HU ,  Yubao ZHOU ,  Li FANG ,  Haiwen HU ,  Zhongjun XU

    IPC分类号： C07D319/16 ,  C07D491/056

    CPC分类号： C07D319/16 ,  C07D491/056

    摘要： The present invention relates to a method for preparing GLP-1 receptor agonist, specifically relates to an industrialized method for preparing a GLP-1 receptor agonist (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)propanoic acid dihydrochloride (compound I). The method utilizes compound 1 as the starting material, which undergoes nucleophilic addition, hydrolysis, reduction ammoniation, cyclization, amide condensation, hydrolysis, and salt forming reaction to give compound I. The method for preparing compound I has a total yield of more than 35%, with purity of compound I more than 98%.