((3R,6R)-6-methylpiperidin-3-yl)methanol hydrochloride

• 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: ((3R,6R)-6-methylpiperidin-3-yl)methanol hydrochloride
• 英文别名: [(3r,6r)-6-Methylpiperidin-3-yl]methanol hydrochloride；[(3R,6R)-6-methylpiperidin-3-yl]methanol;hydrochloride
• 化学式: C₇H₁₅NO*ClH
• 分子量: 165.663
• InChiKey: VTNSDDLUAVIRTL-ZJLYAJKPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.79
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  32.3
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  ((3R,6R)-6-methylpiperidin-3-yl)methanol hydrochloride 在 2,6-二甲基吡啶 、 三甲基乙酰氯 、 1-丙基磷酸酐 、 sodium t-butanolate 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.57h， 生成 MK-6096
  参考文献：
  名称：

  Unusual Pyrimidine Participation: Efficient Stereoselective Synthesis of Potent Dual Orexin Receptor Antagonist MK-6096

  摘要：

  An asymmetric synthesis of dual orexin receptor antagonist MK-6096 (1) is described. Key steps for the trans-2,5-disubstituted piperidinyl ether fragment include a biocatalytic transamination, a trans-selective Mukaiyama aldol, and a regioselective pyridyl SNAr process. The pyrimidyl benzoic acid was synthesized via a Negishi coupling and a nitrile hydrolysis. Coupling of the two fragments via a catalytic T3P-mediated amidation completed the synthesis. Unusual behaviors in the hydrolysis of pyrimidyl benzonitrile and the amide coupling of the pyrimidyl benzoic acid are also described.

  DOI：

  10.1021/ol5028249
• 作为产物：
  描述：

  2-methoxyethan-1-aminium (3R,6R)-6-methyl-2-oxopiperidine-3-carboxylate 在 硼烷四氢呋喃络合物 、 盐酸 作用下， 以 正庚烷 、 水 为溶剂， 以70%的产率得到((3R,6R)-6-methylpiperidin-3-yl)methanol hydrochloride
  参考文献：
  名称：

  生物催化转氨和结晶诱导的动态拆分合成（（3 R，6 R）-6-甲基哌啶-3-基）甲醇

  摘要：

  描述了orexin受体拮抗剂MK-6096哌啶核心（（（3 R，6 R）-6-甲基哌啶-3-基）甲醇（3））的不对称合成。由甲基乙烯基酮和丙二酸二乙酯分四个步骤合成目标，总产率为40％。关键操作是实用的结晶诱导的动态拆分，用于将内酰胺酸17的反式/顺式混合物以> 95％de和91％的产率转化为所需的反式内酰胺酸盐。底物内酰胺酸混合物是通过无溶剂迈克尔反应和实际的生物催化转氨过程制备的。

  DOI：

  10.1021/acs.oprd.5b00259

文献信息

• [EN] OXAZOLE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] COMPOSÉS OXAZOLE ANTAGONISTES DES RÉCEPTEURS D'OREXINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2015018029A1

  公开（公告）日：2015-02-12

  The present invention is directed to oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the oxazole compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及氧唑化合物，其为促进睡眠的受体拮抗剂。本发明还涉及所述氧唑化合物在潜在治疗或预防涉及促进睡眠的神经和精神障碍和疾病中的用途。本发明还涉及包含这些化合物的药物组合物。本发明还涉及这些药物组合物在预防或治疗涉及促进睡眠的疾病中的用途。
• [EN] OXAZOLE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR D'OREXINE À BASE D'OXAZOLE
  申请人：MERCK SHARP & DOHME

  公开号：WO2015020930A1

  公开（公告）日：2015-02-12

  The present invention is directed to oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the oxazole compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及氧唑化合物，其为促进素受体的拮抗剂。本发明还涉及所述氧唑化合物在潜在的治疗或预防涉及促进素受体的神经和精神障碍和疾病中的用途。本发明还涉及包含这些化合物的药物组合物。本发明还涉及这些药物组合物在预防或治疗涉及促进素受体的疾病中的用途。
• [EN] PIPERIDINE ISOXAZOLE AND ISOTHIAZOLE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] COMPOSÉS PIPÉRIDINES ISOXAZOLES ET ISOTHIAZOLES ANTAGONISTES DES RÉCEPTEURS DE L'OREXINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2016065585A1

  公开（公告）日：2016-05-06

  The present invention is directed to piperidine isoxazole and isothiazole orexin compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及对脑嗜睡肽受体的拮抗剂——哌啶异噁唑和异噻唑化合物。本发明还涉及所述化合物在潜在的治疗或预防涉及脑嗜睡肽受体的神经和精神障碍和疾病中的用途。本发明还涉及包含这些化合物的组合物。本发明还涉及这些组合物在预防或治疗涉及脑嗜睡肽受体的疾病中的用途。
• [EN] PIPERIDINE OXADIAZOLE AND THIADIAZOLE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES PIPÉRIDINE OXADIAZOLES ET THIADIAZONES DES RÉCEPTEURS DES OREXINES
  申请人：MERCK SHARP & DOHME

  公开号：WO2016069510A1

  公开（公告）日：2016-05-06

  The present invention is directed to piperidine oxadiazole and thiadiazole orexin compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及对脑垂体素受体的拮抗剂哌啶噁二唑和噻二唑化合物。本发明还涉及所述化合物在潜在治疗或预防涉及脑垂体素受体的神经和精神障碍和疾病中的用途。本发明还涉及包含这些化合物的组合物。本发明还涉及这些组合物在预防或治疗涉及脑垂体素受体的疾病中的用途。
• [EN] THIAZOLE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES THIAZOLES DES RÉCEPTEURS DE L'OREXINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2015018027A1

  公开（公告）日：2015-02-12

  The present invention is directed to thiazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the thiazole compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及噻唑化合物，其为促进睡眠的受体拮抗剂。本发明还涉及所述噻唑化合物在潜在治疗或预防涉及促进睡眠受体的神经和精神障碍和疾病中的用途。本发明还涉及包含这些化合物的药物组合物。本发明还涉及这些药物组合物在预防或治疗涉及促进睡眠受体的疾病中的用途。