(S)-(-)-托伐普坦 | 331947-44-5

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (S)-(-)-托伐普坦
• 中文别名: 托伐普坦杂质S异构体
• 英文名称: (S)-tolvaptan
• 英文别名: (S)-7-chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine；(-)-Tolvaptan；Tolvaptan, (S)-；N-[4-[(5S)-7-chloro-5-hydroxy-2,3,4,5-tetrahydro-1-benzazepine-1-carbonyl]-3-methylphenyl]-2-methylbenzamide
• CAS: 331947-44-5
• 化学式: C₂₆H₂₅ClN₂O₃
• 分子量: 448.949
• InChiKey: GYHCTFXIZSNGJT-DEOSSOPVSA-N

物化性质

• 熔点：
  157-164°C
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  苯甲酰氯 、 (S)-(-)-托伐普坦 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以62%的产率得到(S)-5-benzoyloxy-7-chloro-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine
  参考文献：
  名称：

  Practical Synthesis of Both Enantiomers of Vasopressin V2 Receptor Antagonist OPC-41061 Using the Catalytic Asymmetric Hydrogenation

  摘要：

  The optically active enantiomers of 7-chloro-5-hydroxy-l-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine (OPC-41061, 1) were enantioselectively synthesized. The asymmetric transfer hydrogenation of the ketone (2), which is the precursor of 1, gave the corresponding secondary alcohols in good yield and excellent enantiomeric excess.

  DOI：

  10.3987/com-00-s(k)4
• 作为产物：
  描述：

  7-氯-1-[2-甲基-4-[(2-甲基苯甲酰)氨基]苯甲酰基]-5-氧代-2,3,4,5-四氢-1H-1-苯并氮杂卓 在 sodium formate 作用下， 以 aq. phosphate buffer 为溶剂， 反应 36.0h， 以80.4%的产率得到(S)-(-)-托伐普坦
  参考文献：
  名称：

  Efficient biosynthesis of enantiopure tolvaptan by utilizing alcohol dehydrogenase-catalyzed enantioselective reduction

  摘要：

  使用共表达酒精脱氢酶（PsADH）和甲酸脱氢酶（CpFDH）的大肠杆菌整细胞，在双相水-大豆油系统中生物合成对映纯度高的托瓦普坦被证明是一种高效的方法。

  DOI：

  10.1039/c7gc03679e

文献信息

• Efficient and promising asymmetric preparation of enantiopure tolvaptan via transfer hydrogenation with robust catalysts
  作者：Lu Yin、Yourou Zheng、Xian Jia、Xingshu Li、Albert S.C. Chan

  DOI：10.1016/j.tetasy.2010.08.016

  日期：2010.10

  Enantiopure tolvaptan, the first and only oral vasopressin antagonist for hyponatremia has been prepared by using an asymmetric transfer hydrogenation as a key step with HCOOH-Et3N or HCOONa-H2O as the hydrogen donor in open air. Good chemical yields with up to 99% enantioselectivity were obtained with a 1000:1 of S/C in an HCOONa-H2O system. The air and water stable catalysts provide a very promising prospect for industrial application. (C) 2010 Elsevier Ltd. All rights reserved.
• An Efficient Synthesis of Optical Isomers of Vasopressin V2 Receptor Antagonist OPC-41061 by Lipase-catalyzed Enantioselective Transesterification
  作者：Jun Matsubara、Seiji Morita、Hiroshi Yamashita、Kenji Otsubo、Kazuyoshi Kitano、Tadaaki Ohtani、Yoshikazu Kawano、Masahiko Bando、Masaru Kido、Minoru Uchida、Fujio Tabusa

  DOI：10.3987/com-99-s(i)2

  日期：——

  The optically active enantiomers of 7-chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl] -2,3,4,5-tetrahydro-1H-1-benzazepine (OPC-41061, 1) were enantioselectively synthesized. The chiral acetate ((R)-(-)-3) and the chiral alcohol ((S)-(+)-2) were prepared via the resolution of the racemic alcohol ((+/-)-2) using the lipase-mediated transesterification with vinyl acetate. Compounds ((R)-(-)-3) and ((S)-(+)-2) were converted to optically active 1.
• INJECTABLE DEPOT FORMULATION COMPRISING OPTICALLY ACTIVE TOLVAPTAN AND PROCESS OF PRODUCING THE SAME
  申请人：Otsuka Pharmaceutical Co., Ltd.

  公开号：EP2941242B1

  公开（公告）日：2017-02-01
• HETEROCYCLIC COMPOUNDS AS EPHA4 INHIBITORS
  申请人：The Hong Kong University of Science and Technology

  公开号：US20200206220A1

  公开（公告）日：2020-07-02

  New methods and kits for treating diseases caused or exacerbated by overactivated EphA4 signaling are provided. The method includes administering to a subject in need thereof an effective amount of a small molecule compound inhibitor for EphA4 signaling. Also provided are methods for identifying additional compounds as therapeutic agents useful for treating conditions involving overly active EphA4 signaling.
• US9597283B2
  申请人：——

  公开号：US9597283B2

  公开（公告）日：2017-03-21