(1R,4s)-4-(((S)-5-((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)-7,9-dimethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)methyl)cyclohexane-1-carboxylic acid | 1587704-15-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: (1R,4s)-4-(((S)-5-((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)-7,9-dimethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)methyl)cyclohexane-1-carboxylic acid
• CAS: 1587704-15-1
• 化学式: C₃₁H₃₆F₆N₆O₂
• 分子量: 638.656
• InChiKey: IHIUGIVXARLYHP-HXAGEGRHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  45.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  87.38
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  (1r,4r)-methyl 4-((5-((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)-7,9-dimethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)methyl)cyclohexanecarboxylate 在 水 、 sodium hydroxide 作用下， 以 异丙醇 为溶剂， 反应 7.0h， 生成 反式-4-[[(5S)-5-[[[3,5-双(三氟甲基)苯基]甲基](2-甲基-2H-四氮唑-5-基)氨基]-2,3,4,5-四氢-7,9-二甲基-1H-1-苯并氮杂卓-1-基]甲基]环己烷羧酸 、 (1R,4s)-4-(((S)-5-((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)-7,9-dimethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)methyl)cyclohexane-1-carboxylic acid
  参考文献：
  名称：

  Development of a Hydrogenative Reductive Amination for the Synthesis of Evacetrapib: Unexpected Benefits of Water

  摘要：

  For the synthesis of cholesteryl ester transfer protein (CETP) inhibitor evacetrapib, a hydrogenative reductive amination was chosen to join the substituted cyclohexyl subunit to the benzazepine core. The addition of water, which suppressed undesired epimerization without affecting the rate of product formation, was key to the reaction's success. The process was scaled to produce more than 1100 kg of material.

  DOI：

  10.1021/op500025v