(1S,2S,3R,4R)-3-[5-chloro-2-((S)-1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)pyrimidin-4-ylamino]bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide methanesulfonic acid hydrochloride salt | 1354545-57-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (1S,2S,3R,4R)-3-[5-chloro-2-((S)-1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)pyrimidin-4-ylamino]bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide methanesulfonic acid hydrochloride salt
• 英文别名: (1S,2S,3R,4R)-3-[5-chloro-2-((S)-1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)pyrimidin-4-ylamino]bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide mesylate hydrochloride salt；CEP-28122 monomesilate hydrochloride salt；CEP-28122 monomesylate monohydrochloride salt；CEP-28122 Mesylate hydrochloride；(1S,2S,3R,4R)-3-[[5-chloro-2-[[(7S)-4-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide;methanesulfonic acid;hydrochloride
• CAS: 1354545-57-5
• 化学式: CH₄O₃S*C₂₈H₃₅ClN₆O₃*ClH
• 分子量: 671.645
• InChiKey: JMEAVNFZOQOQRX-RMJUCTSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.48
• 重原子数：
  44
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  177
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  甲烷磺酸 、 (2-外,3-外)-3-(2,5-二氯嘧啶-4-基氨基)二环[2.2.1]庚-5-烯-2-甲酰胺 、 1-methoxy-(7S)-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamine 以 丙二醇甲醚 为溶剂， 反应 25.0h， 以87.1%的产率得到(1S,2S,3R,4R)-3-[5-chloro-2-((S)-1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)pyrimidin-4-ylamino]bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide methanesulfonic acid hydrochloride salt
  参考文献：
  名称：

  Development and Scale-Up of an Optimized Route to the ALK Inhibitor CEP-28122

  摘要：

  Evolution of the process strategies to prepare CEP-28122, an anaplastic lymphoma kinase (ALK) inhibitor, is presented. The initial medicinal chemistry route, used for the preparation of key supplies for biological screening, is reviewed. In addition, the process research and development of the final optimized process for manufacture of preclinical and clinical supplies is discussed. Details regarding a blocking group strategy for selective nitration; discovery of a one-pot transfer hydrogenation to effect a reductive amination, nitro group reduction, and dehalogenation; an enzymatic resolution of a critical intermediate; and the discovery of a novel, stable, in situ generated mixed mesylate hydrochloride salt of the API are disclosed.

  DOI：

  10.1021/op200313v

文献信息

• Pharmaceutical Combinations
  申请人：HIRAWAT Samit

  公开号：US20160129003A1

  公开（公告）日：2016-05-12

  A pharmaceutical combination comprising: (a) a phosphatidylinositol-3-kinase inhibitor selected from 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile, 5-(2,6-di-morpholin-4-yl-pyrimidin-4-yl)-4-trifluoromethyl-pyridin-2-ylamine, (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-(4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) or any pharmaceutically acceptable salt thereof, and (b) an anaplastic lymphoma kinase inhibitor, particularly for use in the treatment or prevention of a proliferative disease; uses of such a combination in the treatment or prevention of proliferative diseases; to pharmaceutical compositions of the combination of said therapeutic agents and methods of treating a proliferative disease in a subject comprising administering to said subject a therapeutically effective amount of such a combination.