4-(((6-cyclopropyl-4-(trifluoromethyl)pyridine-2-yl)methoxy)methyl)-4-(4-fluorophenyl)-1-methylpiperidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(((6-cyclopropyl-4-(trifluoromethyl)pyridine-2-yl)methoxy)methyl)-4-(4-fluorophenyl)-1-methylpiperidine
• 英文别名: 2-cyclopropyl-6-(((4-(4-fluorophenyl)-1-methylpiperidin-4-yl)methoxy)methyl)-4-(trifluoromethyl)pyridine；2-cyclopropyl-6-[[4-(4-fluorophenyl)-1-methylpiperidin-4-yl]methoxymethyl]-4-(trifluoromethyl)pyridine
• 化学式: C₂₃H₂₆F₄N₂O
• 分子量: 422.466
• InChiKey: IATCLJLCYDIURR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  25.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(((6-cyclopropyl-4-(trifluoromethyl)pyridine-2-yl)methoxy)methyl)-4-(4-fluorophenyl)-1-methylpiperidine 在 盐酸 作用下， 以 2-甲基四氢呋喃 、 异丙醇 为溶剂， 反应 3.0h， 以0.65 g的产率得到4-(((6-cyclopropyl-4-(trifluoromethyl)pyridine-2-yl)methoxy)methyl)-4-(4-fluorophenyl)-1-methylpiperidin-1-ium chloride
  参考文献：
  名称：

  Development of a Scalable Route to a Dual NK-1/Serotonin Receptor Antagonist

  摘要：

  The evolution of a process for the preparation of a new heterocyclic dual NK1/serotonin receptor antagonist is described. The final synthesis features a telescoped sequence in which an iron(III)-catalyzed Grignard coupling is followed by a benzylic chlorination utilizing trichlorocyanuric acid to construct an unsymmetrical 2,4,6-trisubstituted pyridine. Etherification of a 4,4'-arylhydroxymethane substituted piperidine fragment completes the synthesis of the active pharmaceutical ingredient in 44% overall yield.

  DOI：

  10.1021/op300323k
• 作为产物：
  描述：

  N-Boc-4-哌啶甲酸乙酯 在 lithium aluminium tetrahydride 、 正丁基锂 、 dimethyl sulfide borane 、 potassium-tert-amylate 、 水 、 二环己胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 2-甲基四氢呋喃 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 24.55h， 生成 4-(((6-cyclopropyl-4-(trifluoromethyl)pyridine-2-yl)methoxy)methyl)-4-(4-fluorophenyl)-1-methylpiperidine
  参考文献：
  名称：

  Development of a Scalable Route to a Dual NK-1/Serotonin Receptor Antagonist

  摘要：

  The evolution of a process for the preparation of a new heterocyclic dual NK1/serotonin receptor antagonist is described. The final synthesis features a telescoped sequence in which an iron(III)-catalyzed Grignard coupling is followed by a benzylic chlorination utilizing trichlorocyanuric acid to construct an unsymmetrical 2,4,6-trisubstituted pyridine. Etherification of a 4,4'-arylhydroxymethane substituted piperidine fragment completes the synthesis of the active pharmaceutical ingredient in 44% overall yield.

  DOI：

  10.1021/op300323k

文献信息

• [EN] SUBSTITUTED HETEROCYCLIC ETHERS AND THEIR USE IN CNS DISORDERS<br/>[FR] ÉTHERS HÉTÉROCYCLIQUES SUBSTITUÉS ET LEUR UTILISATION DANS DES TROUBLES DU SYSTÈME NERVEUX CENTRAL
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2009096941A1

  公开（公告）日：2009-08-06

  The invention encompasses compounds of Formula I, including pharmaceutically acceptable salts, their pharmaceutical compositions, and their use in treating CNS disorders.

  这项发明涵盖了公式I的化合物，包括药用盐、它们的药物组合物以及它们在治疗中枢神经系统疾病中的用途。
• SUBSTITUTED HETEROCYCLIC ETHERS AND THEIR USE IN CNS DISORDERS
  申请人：Parker Michael F.

  公开号：US20080027056A1

  公开（公告）日：2008-01-31

  The invention encompasses compounds of Formula I, including pharmaceutically acceptable salts, their pharmaceutical compositions, and their use in treating CNS disorders.

  该发明涵盖了I式化合物，包括药学上可接受的盐、它们的制药组合物以及它们在治疗中枢神经系统疾病方面的用途。
• Substituted Heterocyclic Ethers and Their Use in CNS Disorders
  申请人：Parker Michael F.

  公开号：US20090030040A1

  公开（公告）日：2009-01-29

  The invention encompasses compounds of Formula I, including pharmaceutically acceptable salts, their pharmaceutical compositions, and their use in treating CNS disorders.

  该发明涵盖了I式化合物，包括药学上可接受的盐，它们的制药组合物以及它们在治疗中枢神经系统疾病方面的应用。
• Substituted heterocyclic ethers and their use in CNS disorders
  申请人：Bristol-Myers Squibb Company

  公开号：US08071778B2

  公开（公告）日：2011-12-06

  The invention encompasses compounds of Formula I, including pharmaceutically acceptable salts, their pharmaceutical compositions, and their use in treating CNS disorders.

  该发明涵盖了I式化合物，包括药学上可接受的盐、它们的制药组合物以及它们在治疗中枢神经系统疾病中的应用。
• 4-ARYLALKOXYMETHYL-4-PHENYL PIPERIDINES AND THEIR USE AS NEUROKININ RECEPTOR ANTAGONISTS FOR THE TREATMENT OF CNS DISORDERS
  申请人：Bristol-Myers Squibb Company

  公开号：EP2069328A2

  公开（公告）日：2009-06-17