(1-naphthalen-1-yl-ethyl)-N,N-bis-[3-(3-trifluoromethylphenyl)propyl]amine

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (1-naphthalen-1-yl-ethyl)-N,N-bis-[3-(3-trifluoromethylphenyl)propyl]amine
• 英文别名: Cinacalcet Impurity 8；N-(1-naphthalen-1-ylethyl)-3-[3-(trifluoromethyl)phenyl]-N-[3-[3-(trifluoromethyl)phenyl]propyl]propan-1-amine
• 化学式: C₃₂H₃₁F₆N
• 分子量: 543.595
• InChiKey: BMWNEBVDXWCUKG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.8
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-(3-三氟甲基苯基)丙醇 在 硫酸 、 氢溴酸 、 potassium carbonate 、 苯甲醛 作用下， 以 水 、 甲苯 为溶剂， 反应 48.0h， 生成 (1-naphthalen-1-yl-ethyl)-N,N-bis-[3-(3-trifluoromethylphenyl)propyl]amine
  参考文献：
  名称：

  Industrial Application of the Forster Reaction: Novel One-Pot Synthesis of Cinacalcet Hydrochloride, a Calcimimetic Agent

  摘要：

  Described is a new, practical, and one-pot process, based on the Forster reaction, for the synthesis of cinacalcet hydrochloride (1), a calcimimetic agent and calcium-sensing receptor antagonist. The synthesis comprises the condensation of (1R)-(+)-1-naphthylethyl amine (2) with benzaldehyde (3) followed by reaction of obtained Schiff's base 4 with 1-(3-halopropyl)-3-(trifluoromethyl)-benzene (5) to provide highly unstable iminium salt 6. Subsequent hydrolysis of 6 with water in the same pot yielded cinacalcet. The treatment of cinacalcet with hydrochloric acid during the workup process furnished 1 with an overall yield of around 60%. Our synthetic approach for 1, discussed in this report demonstrates industrial application of the century-old, unexplored name reaction, "Forster's Reaction" or Forster-Decker synthesis.

  DOI：

  10.1021/op200016a

文献信息

• Method For The Preparation Of Cinacalcet And Intermediates And Impurities Thereof
  申请人：Mathad Vijayvitthal Thippannachar

  公开号：US20110319663A1

  公开（公告）日：2011-12-29

  A method for the preparation of Cinacalcet is disclosed comprising treating (R)-1-naphthyl ethylamine with an aromatic aldehyde to form (1R)-1-(2-naphthyl)-N-(aryl methylene)ethanamine derivative of Formula (IV), which is further treated with 1-(3-halopropyl)-3-(trifluoromethyl)benzene of Formula (V) to obtain an iminium salt of Formula (VI), followed by hydrolysis to obtain Cinacalcet free base.

  揭示了一种制备Cinacalcet的方法，包括处理(R)-1-萘乙胺和芳香醛以形成公式(IV)的(1R)-1-(2-萘基)-N-(芳基亚甲基)乙胺衍生物，进一步用公式(V)的1-(3-卤代丙基)-3-(三氟甲基)苯与其反应以获得公式(VI)的亚胺盐，随后水解以获得Cinacalcet的自由基。
• Method for the preparation of cinacalcet and intermediates and impurities thereof
  申请人：Mathad Vijayavitthal Thippannachar

  公开号：US08575395B2

  公开（公告）日：2013-11-05

  A method for the preparation of Cinacalcet is disclosed comprising treating (R)-1-naphthyl ethylamine with an aromatic aldehyde to form (1R)-1-(2-naphthyl)-N-(aryl methylene)ethanamine derivative of Formula (IV), which is further treated with 1-(3-halopropyl)-3-(trifluoromethyl)benzene of Formula (V) to obtain an iminium salt of Formula (VI), followed by hydrolysis to obtain Cinacalcet free base.

  本发明揭示了一种制备西那卡塞的方法，包括将(R)-1-萘乙胺与芳香醛处理以形成公式(IV)的(1R)-1-(2-萘基)-N-(芳基亚甲基)乙胺衍生物，进一步用公式(V)的1-(3-卤代丙基)-3-(三氟甲基)苯与其反应，得到公式(VI)的亚胺盐，随后水解得到西那卡塞游离碱。
• US8575395B2
  申请人：——

  公开号：US8575395B2

  公开（公告）日：2013-11-05
• US8969623B2
  申请人：——

  公开号：US8969623B2

  公开（公告）日：2015-03-03
• Industrial Application of the Forster Reaction: Novel One-Pot Synthesis of Cinacalcet Hydrochloride, a Calcimimetic Agent
  作者：Gorakshanath B. Shinde、Navnath C. Niphade、Shrikant P. Deshmukh、Raghunath B. Toche、Vijayavitthal T. Mathad

  DOI：10.1021/op200016a

  日期：2011.3.18

  Described is a new, practical, and one-pot process, based on the Forster reaction, for the synthesis of cinacalcet hydrochloride (1), a calcimimetic agent and calcium-sensing receptor antagonist. The synthesis comprises the condensation of (1R)-(+)-1-naphthylethyl amine (2) with benzaldehyde (3) followed by reaction of obtained Schiff's base 4 with 1-(3-halopropyl)-3-(trifluoromethyl)-benzene (5) to provide highly unstable iminium salt 6. Subsequent hydrolysis of 6 with water in the same pot yielded cinacalcet. The treatment of cinacalcet with hydrochloric acid during the workup process furnished 1 with an overall yield of around 60%. Our synthetic approach for 1, discussed in this report demonstrates industrial application of the century-old, unexplored name reaction, "Forster's Reaction" or Forster-Decker synthesis.