5-fluoro-2-((3R,6R)-6-methyl-piperidin-3-ylmethoxy)pyridine | 1088993-93-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-fluoro-2-((3R,6R)-6-methyl-piperidin-3-ylmethoxy)pyridine
• 英文别名: 5-fluoro-2-(((3R,6R)-6-methyl-piperidin-3-yl)methoxy)pyridine；5-fluoro-2-{[(3R,6R)-6-methylpiperidin-3-yl]methoxy}pyridine；5-Fluoro-2-(((3R,6R)-6-methylpiperidin-3-yl)methoxy)pyridine；5-fluoro-2-[[(3R,6R)-6-methylpiperidin-3-yl]methoxy]pyridine
• CAS: 1088993-93-4
• 化学式: C₁₂H₁₇FN₂O
• 分子量: 224.278
• InChiKey: GXAUTFQFAVIPJC-NXEZZACHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  34.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-fluoro-2-((3R,6R)-6-methyl-piperidin-3-ylmethoxy)pyridine 在 palladium diacetate 、 四(三苯基膦)钯 、 1,3-双(二苯基膦)丙烷 copper(l) iodide 、 N-羟基-7-氮杂苯并三氮唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 cesium fluoride 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.84h， 生成 methyl 3-(((2R,5R)-5-(((5-fluoropyridin-2-yl)oxy)methyl)-2-methylpiperidin-1-yl)carbonyl)-4-pyrimidin-2-yl-benzoate
  参考文献：
  名称：

  WO2008/147518

  摘要：

  公开号：
• 作为产物：
  描述：

  (2R,5R)-tert-butyl 5-(hydroxymethyl)-2-methylpiperidine-1-carboxylate 在 吡啶 、 caesium carbonate 、 三氟乙酸 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 反应 31.0h， 生成 5-fluoro-2-((3R,6R)-6-methyl-piperidin-3-ylmethoxy)pyridine
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF AN OREXIN RECEPTOR ANTAGONIST
  [FR] PROCÉDÉ DE PRÉPARATION D'UN ANTAGONISTE DES RÉCEPTEURS DE L'OREXINE

  摘要：

  本发明涉及制备吡啶基哌啶化合物的方法，该化合物是俄雷昔腺受体的拮抗剂，对治疗或预防涉及俄雷昔腺受体的神经和精神障碍和疾病具有用处。

  公开号：

  WO2009143033A1

文献信息

• [EN] PROCESS FOR THE PREPARATION OF AN OREXIN RECEPTOR ANTAGONIST<br/>[FR] PROCÉDÉ DE PRÉPARATION D'UN ANTAGONISTE DU RÉCEPTEUR DE L'OREXINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2012058129A1

  公开（公告）日：2012-05-03

  The present invention is directed to processes for preparing a pyridyl piperidine compound which is an antagonist of orexin receptors, and which is useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved.

  本发明涉及制备吡啶基哌啶化合物的方法，该化合物是促进睡眠的受体拮抗剂，可用于治疗或预防涉及促进睡眠的神经和精神障碍和疾病。
• Process for the Preparation of an Orexin Receptor Antagonist
  申请人：Campeau Louis-Charles

  公开号：US20110165632A1

  公开（公告）日：2011-07-07

  The present invention is directed to processes for preparing a pyridyl piperidine compound which is an antagonist of orexin receptors, and which is useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved.

  本发明涉及制备一种吡啶基哌啶类化合物的方法，该化合物是促进睡眠荷尔蒙受体的拮抗剂，并且在治疗或预防神经系统和精神障碍以及促进睡眠荷尔蒙受体参与的疾病方面具有用途。
• PYRIDYL PIPERIDINE OREXIN RECEPTOR ANTAGONISTS
  申请人：Breslin Michael J.

  公开号：US20100168134A1

  公开（公告）日：2010-07-01

  The present invention is. directed to pyridyl piperidine compounds of formula (I) which are antagonists of orexin receptors, and which are useful' in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及式(I)的吡啶基哌啶化合物，其为促进睡眠激素受体的拮抗剂，可用于治疗或预防神经和精神障碍以及涉及促进睡眠激素受体的疾病。本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及促进睡眠激素受体的疾病中的用途。
• Process for the preparation of an orexin receptor antagonist
  申请人：Campeau Louis-Charles

  公开号：US08674093B2

  公开（公告）日：2014-03-18

  The present invention is directed to processes for preparing a pyridyl piperidine compound which is an antagonist of orexin receptors, and which is useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved.

  本发明涉及制备一种吡啶基哌啶化合物的方法，该化合物是一种促进睡眠激素受体拮抗剂，可用于治疗或预防神经和精神障碍以及涉及促进睡眠激素受体的疾病。
• Convergent Kilogram-Scale Synthesis of Dual Orexin Receptor Antagonist
  作者：Mélina Girardin、Stéphane G. Ouellet、Danny Gauvreau、Jeffrey C. Moore、Greg Hughes、Paul N. Devine、Paul D. O’Shea、Louis-Charles Campeau

  DOI：10.1021/op3002678

  日期：2013.1.18

  MK-6096 is an orexin receptor antagonist in clinical trials for the treatment of insomnia. Herein we describe its first kilogram-scale synthesis. Chirality on the a-methylpiperidine core was introduced in a biocatalytic transamination using a three-enzyme system with excellent enantioselectivity (>99% ee). Low diastereoselectivity of the lactam reduction was overcome by development of a camphor sulfonic acid salt formation and dr upgrade. A chemoselective O-alkylation with 5-fluoro-2-hydroxypyridine was optimized and developed. Overall, 1.2 kg of MK-6069 was prepared in nine steps and 13% overall yield.