2-cyclohexyl-1,2,3,4-tetrahydroquinoline | 123629-22-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 2-cyclohexyl-1,2,3,4-tetrahydroquinoline
• 英文别名: (RS)-2-cyclohexyl-1,2,3,4-tetrahydroquinoline；2-Cyclohexyl-1,2,3,4-tetrahydro-chinolin
• CAS: 123629-22-1
• 化学式: C₁₅H₂₁N
• 分子量: 215.338
• InChiKey: NWKAUHWCWIGFTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-cyclohexyl-1,2,3,4-tetrahydroquinoline 在 1-phenyl-N-(3,4,5-trimethoxyphenyl)ethan-1-imine 、 C₅₀H₅₉O₄P 作用下， 以 甲苯 为溶剂， 反应 72.0h， 以50%的产率得到(S)-2-cyclohexyl-1,2,3,4-tetrahydroquinoline
  参考文献：
  名称：

  Chiral phosphoric acid catalyzed oxidative kinetic resolution of cyclic secondary amine derivatives including tetrahydroquinolines by hydrogen transfer to imines

  摘要：

  四氢喹啉与酮亚胺在手性磷酸存在下的标题反应以高效转化和优异对映选择性进行。

  DOI：

  10.1039/c5cc06436h
• 作为产物：
  描述：

  2-苯基喹啉 在 盐酸 、 Pt/Al₂O₃ 、 colloid 作用下， 60.0 ℃ 、202.65 kPa 条件下， 生成 2-cyclohexyl-1,2,3,4-tetrahydroquinoline
  参考文献：
  名称：

  Skita; Wulff, Chemische Berichte, 1926, vol. 59, p. 2691

  摘要：

  DOI：

文献信息

• The Remarkable Effect of a Simple Ion: Iodide-Promoted Transfer Hydrogenation of Heteroaromatics
  作者：Jianjun Wu、Chao Wang、Weijun Tang、Alan Pettman、Jianliang Xiao

  DOI：10.1002/chem.201201517

  日期：2012.7.27

  I can do it! Accelerated by simple iodide ions, rhodium‐catalysed transfer hydrogenation can be readily performed on quinolines, isoquinolines and quinoxalines, affording the tetrahydro products in high yields with low catalyst loading (see scheme).

  我能做到！通过简单的碘离子加速，铑催化的转移加氢反应可轻松地在喹啉，异喹啉和喹喔啉上进行，从而以高收率和低催化剂负载量提供四氢产物（参见方案）。
• Photocatalytic Hydroaminoalkylation of Styrenes with Unprotected Primary Alkylamines
  作者：Hannah E. Askey、James D. Grayson、Joshua D. Tibbetts、Jacob C. Turner-Dore、Jake M. Holmes、Gabriele Kociok-Kohn、Gail L. Wrigley、Alexander J. Cresswell

  DOI：10.1021/jacs.1c07401

  日期：2021.10.6

  moderately electron-rich aryl groups. A broad range of functionalities are tolerated, and the reactions can be run on multigram scale in continuous flow. The method is applied to a concise, protecting-group-free synthesis of the blockbuster drug Fingolimod, as well as a phosphonate mimic of its in vivo active form (by iterative α-C–H functionalization of ethanolamine). The reaction can also be sequenced

  苯乙烯的催化分子间氢氨烷基化 (HAA) 为药理学相关的 γ-芳胺提供了强大的断裂作用，但目前的方法不能利用未受保护的伯烷基胺作为原料。金属催化的 HAA 方案对胺伴侣上的 α-取代也高度敏感，并且不存在通过这种方法合成 α-叔 γ-芳胺的催化解决方案。我们报告了使用有机光氧化还原催化解决这些问题的方法，能够直接、模块化和可持续地制备α-（二）取代的γ-芳胺，包括具有挑战性的电子中性和适度富电子的芳基。可以耐受多种功能，并且反应可以在连续流程中以数克规模运行。该方法适用于重磅药物芬戈莫德及其体内活性形式的膦酸盐模拟物的简洁、无保护基合成（通过乙醇胺的迭代 α-C-H 官能化）。该反应还可以通过分子内N -芳基化进行测序，以提供获得有价值的（螺环）1,2,3,4-四氢喹啉和 1,2,3,4-四氢萘啶的通用和模块化途径。机理和动力学研究支持叠氮基自由基对烷基胺的不可逆氢原子转移活化以及自由基链
• [EN] TRICYCLIC 1-[(3-INDOL-3-YL)CARBONYL] PIPERAZINE DERIVATIVES AS CANNABINOID CB1 RECEPTOR AGONISTS<br/>[FR] DERIVES TRICYCLIQUES DE PIPERAZINE 1-[(3-INDOL-3-YL)CARBONYL] UTILES EN TANT QU'AGONISTES DU RECEPTEUR CANNABINOIDE CB1
  申请人：AKZO NOBEL NV

  公开号：WO2005058327A1

  公开（公告）日：2005-06-30

  The invention relates to tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivative having the general Formula (I) wherein X is CH2, O or S; R represents 1-3 substituents independently selected from H, (C1-4)alkyl, (C1-4)alkyloxy and halogen; R1 is (C5-8)cycloalkyl; R2 is H or (C1-4)alkyl; R3, R3´, R4’ R4’, R5, R5’ and R6’ are independently hydrogen or (C1-4)-alkyl, optionally substituted with (C1-4)alkyloxy, OH or halogen; R6 is hydrogen or (C1-4)alkyl, optionally substituted with (C1-4)alkyloxy, OH or halogen; or R6 forms together with R7 a 4-7 membered saturated heterocyclic ring, optionally containing a further heteroatom selected from O and S; R7 forms together with R6 a 4-7 membered saturated heterocydic ring, optionally containing a further heteroatom selected from O and S; or R7 is H, (C1-4)alkyl or (C3-5)cycloalkyl, the alkyl groups being optionally substituted with OH, halogen or (C1-4)alkyloxy; or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivatives, and to the use of these derivatives in the treatment of pain, such as peri-operative pain, chronic pain neuropathic pain, cancer pain, and pain and spasticity associated with multiple sclerosis.

  该发明涉及具有通式（I）的三环1-[(吲哚-3-基)羰基]哌嗪衍生物，其中X为CH2、O或S；R代表1-3个取自H、(C1-4)烷基、(C1-4)烷氧基和卤素的取代基；R1为(C5-8)环烷基；R2为H或(C1-4)烷基；R3、R3'、R4'、R4'、R5、R5'和R6'独立地为氢或(C1-4)烷基，可选地取代为(C1-4)烷氧基、OH或卤素；R6为氢或(C1-4)烷基，可选地取代为(C1-4)烷氧基、OH或卤素；或R6与R7一起形成一个含有O和S等进一步杂原子的4-7元饱和杂环；R7与R6一起形成一个含有O和S等进一步杂原子的4-7元饱和杂环；或R7为H、(C1-4)烷基或(C3-5)环烷基，烷基基团可选地取代为OH、卤素或(C1-4)烷氧基；或其药学上可接受的盐。该发明还涉及包含所述三环1-[(吲哚-3-基)羰基]哌嗪衍生物的药物组合物，并且涉及在治疗疼痛，如围手术疼痛、慢性疼痛、神经痛、癌症疼痛以及与多发性硬化相关的疼痛和痉挛中使用这些衍生物。
• pH-Regulated Asymmetric Transfer Hydrogenation of Quinolines in Water
  作者：Chao Wang、Chaoqun Li、Xiaofeng Wu、Alan Pettman、Jianliang Xiao

  DOI：10.1002/anie.200902570

  日期：2009.8.17

  In buffered water, a broad range of quinoline derivatives underwent asymmetric transfer hydrogenation in air with the rhodium catalyst 1 and sodium formate as the hydrogen source to furnish synthetically important 1,2,3,4‐tetrahydroquinolines with excellent enantioselectivities (see scheme; R=H, Me, F, Cl, Br, OMe; R′=alkyl, aryl).

  在缓冲水中，各种各样的喹啉衍生物在空气中以铑催化剂1和甲酸钠作为氢源进行不对称转移加氢，以提供具有重要对映选择性的重要合成1,2,3,4-四氢喹啉（参见方案； R = H，Me，F，Cl，Br，OMe； R'＝烷基，芳基）。
• Design, synthesis, and structure–activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists
  作者：Takao Kiyoi、Mark York、Stuart Francis、Darren Edwards、Glenn Walker、Andrea K. Houghton、Jean E. Cottney、James Baker、Julia M. Adam

  DOI：10.1016/j.bmcl.2010.06.067

  日期：2010.8

  Novel tricyclic indole-3-carboxamides were synthesized as structurally restricted analogs of bicyclic indoles, and found to be potent CB1 cannabinoid receptor agonists. The CB1 agonist activity depended on the absolute configuration of the chiral center of the tricyclic ring. The preferred enantiomer was more potent than the structurally unconstrained lead compound. Structure–activity relationships

  新型三环吲哚-3-羧酰胺被合成为双环吲哚的结构受限类似物，并被发现是有效的CB1大麻素受体激动剂。CB1激动剂活性取决于三环手性中心的绝对构型。优选的对映异构体比结构不受限制的铅化合物更有效。还研究了吲哚C-3位置酰胺侧链的结构活性关系。