(S)-2-[2-(1-methyl-2-piperidinyl)ethyl]benzenamine (1R,3S)-(+)-camphoric acid salt | 62414-73-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: (S)-2-[2-(1-methyl-2-piperidinyl)ethyl]benzenamine (1R,3S)-(+)-camphoric acid salt
• 英文别名: (s)-2-[2-(1-Methyl-2-piperidinyl)ethyl]-benzenamine (1r,3s)-(+)-camphoric acid salt；2-[2-[(2S)-1-methylpiperidin-2-yl]ethyl]aniline;(1R,3S)-1,2,2-trimethylcyclopentane-1,3-dicarboxylic acid
• CAS: 62414-73-7
• 化学式: C₁₀H₁₆O₄*C₁₄H₂₂N₂
• 分子量: 418.577
• InChiKey: JLBRWEQSSUKNHM-VIMBSDIGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.28
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-[2-(1-methyl-2-piperidinyl)ethyl]benzenamine (1R,3S)-(+)-camphoric acid salt 在 potassium carbonate 、 sodium hydroxide 作用下， 以 醋酸异丙酯 、 水 为溶剂， 反应 2.0h， 生成 Iferanserin
  参考文献：
  名称：

  Development of a Scalable Synthesis of a Serotonin Receptor Antagonist

  摘要：

  An efficient process was developed for the manufacture of MSA100, a serotonin receptor antagonist, via a five-step synthetic route furnishing a high quality of active pharmaceutical ingredient. Highlights of this synthesis include: (1) replacing carcinogenic methyl iodide with methyl p-toluenesulfonate as the methylating reagent; (2) a hydrogenation protocol with optimized temperature, pressure, and mass-transfer conditions that avoided one side product and reduced the other one effectively; (3) chemical resolution employing D-camphoric acid in a mixed-solvent system; (4) amidation under anhydrous conditions for controlling a Michael adduct impurity; and (5) plausible mechanisms for the formation of side products.

  DOI：

  10.1021/op5003402
• 作为产物：
  描述：

  (E)-2-(2-nitrostyryl)pyridine 在 10% Pt/activated carbon 、 氢气 、 sodium hydroxide 作用下， 以 甲醇 、 醋酸异丙酯 、 水 、 乙腈 为溶剂， 30.0~82.0 ℃ 、517.12 kPa 条件下， 反应 24.0h， 生成 (S)-2-[2-(1-methyl-2-piperidinyl)ethyl]benzenamine (1R,3S)-(+)-camphoric acid salt
  参考文献：
  名称：

  Development of a Scalable Synthesis of a Serotonin Receptor Antagonist

  摘要：

  An efficient process was developed for the manufacture of MSA100, a serotonin receptor antagonist, via a five-step synthetic route furnishing a high quality of active pharmaceutical ingredient. Highlights of this synthesis include: (1) replacing carcinogenic methyl iodide with methyl p-toluenesulfonate as the methylating reagent; (2) a hydrogenation protocol with optimized temperature, pressure, and mass-transfer conditions that avoided one side product and reduced the other one effectively; (3) chemical resolution employing D-camphoric acid in a mixed-solvent system; (4) amidation under anhydrous conditions for controlling a Michael adduct impurity; and (5) plausible mechanisms for the formation of side products.

  DOI：

  10.1021/op5003402
• 作为试剂：
  描述：

  D-樟脑酸 、 、 乙醇 、 、 2-(邻-氨基苯乙基)-1-甲基哌啶 在 氮气 、 异丙醇 、 (S)-2-[2-(1-methyl-2-piperidinyl)ethyl]benzenamine (1R,3S)-(+)-camphoric acid salt 、 polypropylene 作用下， 以 异丙醇 为溶剂， 20.0~90.0 ℃ 、533.29 kPa 条件下， 反应 8.75h， 以to obtain a constant weight (LOD<1%, 4 h) of 15.14 g of crude (S)-2-[2-(1-methyl-2-piperidinyl)ethyl]-benzenamine (1R,3S)-(+)-camphoric acid salt (1:1) as a white solid (enantiomeric purity: S:R=98.6:1.4)的产率得到(S)-2-[2-(1-methyl-2-piperidinyl)ethyl]benzenamine (1R,3S)-(+)-camphoric acid salt
  参考文献：
  名称：

  Organic Compounds

  摘要：

  本发明涉及一种合成(S)-2’[2-1-(甲基-2-哌啶基)乙基]肉桂酰亚胺(I)或其盐或药物可接受的前药的过程。

  公开号：

  US20090247581A1

文献信息

• WO2007/111706
  申请人：——

  公开号：——

  公开（公告）日：——
• Org. Process Res. Dev. 2015, 19, 290-295
  作者：

  DOI：——

  日期：——
• Development of a Scalable Synthesis of a Serotonin Receptor Antagonist
  作者：Mahavir Prashad、Yugang Liu、Wen-Chung Shieh、Frank Schaefer、Bin Hu、Michael Girgis

  DOI：10.1021/op5003402

  日期：2015.1.16

  An efficient process was developed for the manufacture of MSA100, a serotonin receptor antagonist, via a five-step synthetic route furnishing a high quality of active pharmaceutical ingredient. Highlights of this synthesis include: (1) replacing carcinogenic methyl iodide with methyl p-toluenesulfonate as the methylating reagent; (2) a hydrogenation protocol with optimized temperature, pressure, and mass-transfer conditions that avoided one side product and reduced the other one effectively; (3) chemical resolution employing D-camphoric acid in a mixed-solvent system; (4) amidation under anhydrous conditions for controlling a Michael adduct impurity; and (5) plausible mechanisms for the formation of side products.
• Organic Compounds
  申请人：Prashad Mahavir

  公开号：US20090247581A1

  公开（公告）日：2009-10-01

  The present invention relates to a process for the synthesis of (S)-2′[2-1-(methyl-2-piperidyl) ethyl] cinnamanilide (I) or salts or pharmaceutically acceptable prodrugs thereof:

  本发明涉及一种合成(S)-2’[2-1-(甲基-2-哌啶基)乙基]肉桂酰亚胺(I)或其盐或药物可接受的前药的过程。