5,6-dihydroindolo[2,1-a]isoquinoline-12-carbaldehyde | 162851-60-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5,6-dihydroindolo[2,1-a]isoquinoline-12-carbaldehyde
• CAS: 162851-60-7
• 化学式: C₁₇H₁₃NO
• 分子量: 247.296
• InChiKey: AFQRLNHTLTVPPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  22
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5,6-dihydroindolo[2,1-a]isoquinoline-12-carbaldehyde 在 lithium aluminium tetrahydride 、 ammonium acetate 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 N-[2-(5,6-Dihydro-indolo[2,1-a]isoquinolin-12-yl)-ethyl]-acetamide
  参考文献：
  名称：

  Mapping the Melatonin Receptor. 6. Melatonin Agonists and Antagonists Derived from 6H-Isoindolo[2,1-a]indoles, 5,6-Dihydroindolo[2,1-a]isoquinolines, and 6,7-Dihydro-5H-benzo[c]azepino[2,1-a]indoles

  摘要：

  6H-Isoindolo[2,1-a]indoles (5, 7, 10, 13), 5,6-dihydroindolo[2,1-a]isoquinolines (20, 21), and 6,7-dihydro-5H-benzo[c]azepino[2,1-a]indoles (23, 25, 27, 30) have been prepared as melatonin analogues to investigate the nature of the binding site of the melatonin receptor. The affinity of analogues was determined in a radioligand binding assay using cloned human mt(1) and MT2 receptor subtypes expressed in NIH 3T3 cells. Agonist and antagonist potency was measured using the pigment aggregation response of a clonal line of Xenopus laevis melanophores. The 2-methoxyisoindolo[2,1-a]indoles (7a-d) showed much higher binding affinities than the parent isoindoles (5a-e), and whereas 7a-c were agonists in the functional assay, 7d and 5a-e were antagonists. The 2-ethoxyisoindolo[2,1-a]indoles (10a-d) showed reduced binding affinities compared to their methoxy analogues, while the 5-chloro derivative 13 showed a considerable reduction in binding affinity and potency compared to 7a. The 10-methoxy-5,6-dihydroindolo[2,1-a]isoquinolines (21a-c) had higher binding affinities than the corresponding parent indoloisoquinolines (20a-c) in the human receptor subtypes, and the parent compounds were antagonists whereas the 10-methoxy derivatives were agonists in the functional assay. The N-cyclobutanecarbonyl derivatives of both the parent (20d) and 10-methoxyl (21d) series had similar binding affinities and were both antagonists with similar potencies. The 11-methoxy-6,7-5H-benzo[c]azepino[2,1-a]indoles (25a-d) had higher binding affinities than the corresponding parent compounds (23a-d) at the MT2 receptor but similar affinities at the mt(1) site; all of the compounds were antagonists in the functional assay. Changing 11-methoxy for 11-ethoxy decreased the binding affinity slightly, and this was more evident at the MT2 receptor. All of the derivatives investigated had either the same or a greater affinity for the human MT2 receptor compared to the mt(1) receptor (range 1:1-1:132). This suggests that the mt(1) and MT2 receptor pockets differ in their ability to accommodate alkyl groups in the indole nitrogen region of the melatonin molecule. Two compounds (7c and 25c) were tested in functional assays on recombinant mt(1) and MT2 melatonin receptors. Compound 7c is a potent agonist with some selectivity (44-fold) for the MT2 receptor, while 25c is an MT2-preferring antagonist. Increasing the carbon chain length between N-1 of indole and the 2-phenyl group from n = 1 through n = 3 leads to a fairly regular decrease in the binding affinity, but, remarkably, when n = 3, it converts the methoxy compounds from melatonin agonists to antagonists. The Xenopus melatonin receptor thus cannot accommodate an N-n-alkyl chain attached to a 2-phenyl substituent with n > 2 in the required orientation to induce or stabilize the active receptor conformation.

  DOI：

  10.1021/jm980684+
• 作为产物：
  描述：

  1-<2-(2-bromophenyl)-2-oxoethyl>-1H-indole-3-carboxaldehyde 在 四(三苯基膦)钯 、 potassium acetate 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.0h， 生成 5,6-dihydroindolo[2,1-a]isoquinoline-12-carbaldehyde
  参考文献：
  名称：

  Desarbre, Eric; Merour, Jean-Yves, Heterocycles, 1995, vol. 41, # 9, p. 1987 - 1998

  摘要：

  DOI：

文献信息

• Intramolecular Oxidative C−H Coupling for Medium-Ring Synthesis
  作者：Didier G. Pintori、Michael F. Greaney

  DOI：10.1021/ja1090854

  日期：2011.2.9

  An oxidative C-H coupling is described for medium-ring synthesis.

  描述了用于中环合成的氧化 CH 偶联。
• An efficient approach to 1,2,3-trisubstituted indole via rhodium catalyzed carbene C_sp3–H bond insertion
  作者：Mei-Hua Shen、Ying-Peng Pan、Zhi-Hong Jia、Xin-Tao Ren、Ping Zhang、Hua-Dong Xu

  DOI：10.1039/c5ob00085h

  日期：——

  A method for convenient synthesis ofN-alkyl-2-aryl-indole-3-carbaldehydeviacarbene C–H bond insertion.

  一种通过卡宾C-H键插入方便地合成N-烷基-2-芳基吲哚-3-甲醛的方法。
• Gold-Catalyzed Bicyclic Annulations of <i>N</i>-(<i>o</i>-Alkynylphenyl)imines with α-Diazo Esters to Form 5,6-Dihydroindolo[2,1-<i>a</i>]isoquinolines
  作者：Akshay Subhash Narode、Rai-Shung Liu

  DOI：10.1021/acs.orglett.2c00450

  日期：2022.3.25

  One-pot synthesis of 5,6-dihydroindolo[2,1-a]isoquinolines from gold-catalyzed annulations between N-(o-alkynylphenyl)imines and α-diazo esters is described. This cascade reaction involves an initial attack of the diazo ester at the imine to form cis-aziridine, followed by stereoselective [3 + 3]-annulations with the tethered arylalkyne. We have employed this new catalysis to prepare one bioactive

  描述了从N- ( o-炔基苯基) 亚胺和 α-重氮酯之间的金催化环化合成 5,6-二氢吲哚[2,1- a ] 异喹啉的一锅法。这种级联反应涉及重氮酯在亚胺上的初始攻击以形成顺式-氮丙啶，然后是立体选择性的 [3 + 3]-环化与束缚的芳基炔烃。我们采用这种新的催化剂制备了一种具有生物活性的 5,6-二氢吲哚[2,1- a ]异喹啉分子。
• Synthesis of Dihydroindoloisoquinolines through Copper‐Catalyzed Cross‐Dehydrogenative Coupling of Tetrahydroisoquinolines and Nitroalkanes
  作者：Iris Martín‐García、Francisco Alonso

  DOI：10.1002/chem.201805137

  日期：2018.12.17

  organic chemistry; the corresponding β‐nitroamines are generally formed irrespective of the catalysis and activation mode utilized. A quite distinct behavior was observed when the reaction was catalyzed by copper nanoparticles supported on titania, leading to the formation of 5,6‐dihydroindolo[2,1‐a]isoquinolines with high selectivity and good yields. A meticulous reaction mechanism is proposed, based

  最近，四氢异喹啉与硝基烷烃的交叉脱氢反应已成为有机化学中广泛研究的反应。无论使用何种催化和活化方式，通常都会形成相应的β-硝基胺。当负载在二氧化钛上的铜纳米颗粒催化反应时，观察到非常不同的行为，导致形成具有高选择性和高收率的5,6-二氢吲哚并[2,1- a ]异喹啉。在实验的基础上，提出了一种精细的反应机理，并讨论了这些化合物的关键化学修饰。显然，催化剂的有效性在于其纳米结构的特性，胜过了商用铜催化剂的活性。
• Intramolecular Photochemical Cross-Coupling Reactions of 3-Acyl-2-haloindoles and 2-Chloropyrrole-3-carbaldehydes with Substituted Benzenes
  作者：Shen-Ci Lu、Xi-Xia Zhang、Zong-Jun Shi、Yu-Wei Ren、Bing Li、Wei Zhang

  DOI：10.1002/adsc.200900540

  日期：2009.11

  Highly efficient syntheses of indolo[2,1-a]isoquinolines, indolo[2,1-a][2]benzazepines, pyrrolo[2,1-a]isoquinolines and pyrrolo[1,2-a]benzazepines in excellent yields have been achieved by the intramolecular photochemical cross-coupling reactions of 3-acyl-2-halo-N-(ω-arylalkyl)indoles and 2-chloro-N-(ω-arylalkyl)pyrrole-3-carbaldehydes in acetone. A new heterocyclic ring system – pyrrolo[1,2-d][1

  高效合成吲哚[2,1- a ]异喹啉，吲哚[ 2,1- a ] [2]苯并ze庚因，吡咯并[2,1- a ]异喹啉和吡咯并[1,2- a ]苯并ze庚因通过3-酰基-2-卤代-N-（ω-芳基烷基）吲哚和2-氯-N-（ω-芳基烷基）吡咯-3-甲醛在丙酮中的分子内光化学交叉偶联反应获得了上述结果。通过2-氯-N-（2-苯氧基乙基）吡咯-3的光环化，在这项工作中还首次构建了一种新的杂环系统吡咯并[1,2- d ] [1,4]苯并benzo氮平-甲醛