ethyl 6-chloro-1-methyl-1H-indole-2-carboxylate | 43142-81-0

• 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: ethyl 6-chloro-1-methyl-1H-indole-2-carboxylate
• 英文别名: ethyl 6-chloro-1-methylindole-2-carboxylate；6-chloro-1-methyl-indole-2-carboxylic acid ethyl ester；Ethyl-(6-chloro-1-methylindol)-2-carboxylat
• CAS: 43142-81-0
• 化学式: C₁₂H₁₂ClNO₂
• 分子量: 237.686
• InChiKey: QMVJTCIUKISOGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  ethyl 6-chloro-1-methyl-1H-indole-2-carboxylate 在 四氯化钛 sodium hydroxide 、 溶剂黄146 作用下， 以 水 、 1,2-二氯乙烷 为溶剂， 生成 ethyl 7-chloro-3-(3-chlorophenyl)-5-methyl-4-oxo-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-carboxylate
  参考文献：
  名称：

  4-oxo-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-carboxamide derivatives, preparation and therapeutic use

  摘要：

  具有亲和力的外周苯二氮卓受体的4-氧代-3,5-二氢-4H-吡啶并［4,5-b］吲哚-1-甲酰胺衍生物对于预防或治疗外周神经病变以及治疗中枢神经变性疾病是有用的。

  公开号：

  US06451795B1
• 作为产物：
  描述：

  (4-氯-2-硝基-苯基)-丙酮酸 在 硫酸 、 氨 、 iron(II) sulfate 作用下， 以 二甲基亚砜 为溶剂， 生成 ethyl 6-chloro-1-methyl-1H-indole-2-carboxylate
  参考文献：
  名称：

  Indoline analogs of idazoxan: potent .alpha.2-antagonists and .alpha.1-agonists

  摘要：

  The synthesis and alpha-adrenergic activity of a series of substituted 2-imidazolinylindolines are described. Substitution in the indoline ring generated compounds with a spectrum of adrenoceptor antagonist/agonist profiles that proved sensitive to both the nature and position of the substituent. Many of the derivatives possess greater presynaptic antagonist potency than the corresponding benzodioxan 1, dihydrobenzofuran 2, and indan 3 analogues; however, this alpha 2-antagonism is often accompanied by alpha 1-agonist activity. It was not possible to separate alpha 2-antagonist from alpha 1-agonist properties in this series. Compounds of most interest proved to be the N-ethyl 6, 5-chloro-N-methyl 18, and 5-chloro-N-ethyl 23 derivatives, all being potent alpha 2-antagonists and alpha 1-agonists. Substitution at the 4- and 7-position of the indoline ring generally gave compounds with nonselective agonist properties.

  DOI：

  10.1021/jm00400a009

文献信息

• Synthesis, Biological Evaluation, and Structure−Activity Relationships of 3-Acylindole-2-carboxylic Acids as Inhibitors of the Cytosolic Phospholipase A₂
  作者：Matthias Lehr

  DOI：10.1021/jm960863w

  日期：1997.8.1

  Replacement of the carboxylic acid group in position 2 of the indole with an acetic or propionic acid substituent led to a decrease of inhibitory potency. Enzyme inhibition was optimal when the acyl residue in position 3 had a length of 12 or more carbons. Conformational restriction of the acyl residue did not influence activity. Introduction of alkyl chains at position 1 of the indole with 8 or more carbons

  制备3-酰基吲哚-2-羧酸衍生物，并评价其抑制完整牛血小板的胞质磷脂酶A2的能力。为了定义酶抑制的结构要求，对羧酸基，酰基残基和位置1的部分进行了系统修饰。此外，将不同的取代基引入到吲哚的苯基部分中。用乙酸或丙酸取代基取代吲哚的2位上的羧酸基导致抑制效力的降低。当位置3上的酰基残基具有12个或更多碳原子时，酶抑制作用最佳。酰基残基的构象限制不影响活性。在具有8个或更多个碳的吲哚的位置1处引入烷基链导致活性降低。然而，发现用羧酸部分取代此类化合物的ω-甲基会显着增加抑制效力。在测试的吲哚衍生物中，1- [2-（4-羧基苯氧基）乙基] -3-十二烷酰基吲哚-2-羧基酸（29b）具有最高的效价。IC50为0.5 microM，它的活性比标准cPLA2抑制剂花生四烯酸三氟甲基酮（IC50：11 microM）高约20倍。
• Zinc-Catalyzed Alkyne Oxidation/CH Functionalization: Highly Site-Selective Synthesis of Versatile Isoquinolones and β-Carbolines
  作者：Long Li、Bo Zhou、Yong-Heng Wang、Chao Shu、Yi-Fei Pan、Xin Lu、Long-Wu Ye

  DOI：10.1002/anie.201502553

  日期：2015.7.6

  An efficient zinc(II)‐catalyzed alkyne oxidation/CH functionalization sequence was developed, thus leading to highly site‐selective synthesis of a variety of isoquinolones and β‐carbolines. Importantly, in contrast to the well‐established gold‐catalyzed intermolecular alkyne oxidation, over‐oxidation can be completely suppressed in this system and the reaction most likely proceeds by a Friedel–Crafts‐type

  一种有效的锌（II） -催化的炔氧化/ C  ħ官能序列被开发，因此导致多种异喹诺酮和β咔啉的高度位点选择性合成。重要的是，与公认的金催化的分子间炔烃氧化相反，该体系中的过氧化可以被完全抑制，并且反应很可能通过Friedel-Crafts型途径进行。描述了力学研究和理论计算。
• PYRIDAZINOINDOLE COMPOUNDS AND METHODS FOR PET IMAGING
  申请人：Vanderbilt University

  公开号：US20160220704A1

  公开（公告）日：2016-08-04

  Embodiments of the invention include a novel synthesis of the translocator protein (TSPO) ligands, and methods of imaging a molecular events. Also disclosed are compounds for treatment of diseases, including cancer.

  该发明的实施例包括一种新型的转位蛋白（TSPO）配体的合成方法，以及分子事件成像的方法。还披露了用于治疗疾病，包括癌症的化合物。
• 4-Oxo-3,5-dihydro-4H-pyridazino[4,5-b]-indole-1-acetamide derivatives, their preparation and their application in therapy
  申请人：Sanofi-Synthelabo

  公开号：US06262045B1

  公开（公告）日：2001-07-17

  Compounds of general formula (I) in which X represents a hydrogen or halogen atom or a methyl, methoxy or phenylmethoxy group, Y represents a hydrogen atom, 1 or 2 halogen atoms or a hydroxyl, methoxy, nitro or methyl group, R1 represents a hydrogen atom or a (C1-C4)alkyl group, R2 and R3 each represent a hydrogen atom, a (C1-C4)alkyl group or a phenylmethyl group or else R2 and R3 form, with the nitrogen atom which carries them, an azetidinyl, pyrrolidinyl, 3-ethoxypyrrolidinyl, piperidinyl, morpholinyl, 4-methylpiperazinyl or 1,3-thiazolidinyl group. Application in therapeutics.

  通式（I）的化合物中，其中X代表氢或卤素原子或甲基、甲氧基或苯甲氧基基团，Y代表氢原子、1或2个卤素原子或羟基、甲氧基、硝基或甲基基团，R1代表氢原子或（C1-C4）烷基基团，R2和R3各自代表氢原子、（C1-C4）烷基基团或苯甲基基团，或者R2和R3与携带它们的氮原子形成氮杂环丙氧基环、吡咯环、3-乙氧基吡咯环、哌啶环、吗啉环、4-甲基哌嗪环或1,3-噻唑烷基团。在治疗学中的应用。
• Abnormal Fischer indolization and its related compounds. XXII. Fischer indolization of ethyl pyruvate 2-(2-chloro- and 2,6-dichlorophenyl)methylhydrazones.
  作者：Hisashi ISHII、Yasuoki MURAKAMI、Tsutomu ISHIKAWA

  DOI：10.1248/cpb.38.597

  日期：——

  The Fischer indolization of ethyl pyruvate 2-(2-chlorophenyl)methylhydrazone (17) with HCl/EtOH proceeded rapidly to give six 1-methylindoles, ethyl 7-chloro (19), 6-chloro (22), and unsubstituted (24)-1-methylindole-2-car-boxylates, and dichloro derivatives (21, 23, and 26), whereas no indolization had occurred with the correspinding NH-hydrazone, as described in a previous paper. This result shows that the abnormal Fischer indolization of 2-chloro-phenylhydrazones with HCl/EtOH occurred in an ortho-C6 fashion, in the same manner as that of the corresponding 2-methoxyphenylhydrazones (1 and 2).The Fischer indolization of ethyl pyruvate 2-(2, 6-dichlorophenyl)methylhydrazone (18) with HCl/EtOH did not occur at all, whereas the reaction with ZnCl2/AcOH gave a low yield of ethyl 5, 7-dichloro-3-methylindole-2-carboxylate (36), which was formed by migration of the N-methyl group during Fischer indolization.

  乙酰丙酮的Fischer吲哚化反应中，2-(2-氯苯基)甲基肼酮（17）与HCl/乙醇反应迅速生成六种1-甲基吲哚，包括乙基7-氯（19）、6-氯（22）和未取代（24）-1-甲基吲哚-2-羧酸酯，以及二氯衍生物（21、23和26），而与相应的NH-肼酮之间并未发生吲哚化反应，如前一篇论文所述。该结果表明，2-氯苯基肼酮与HCl/乙醇发生了异常的Fischer吲哚化反应，呈现出ortho-C6的方式，与相应的2-甲氧基苯基肼酮（1和2）的反应方式相同。乙酰丙酮2-(2, 6-二氯苯基)甲基肼酮（18）与HCl/乙醇的Fischer吲哚化反应完全未发生，而与ZnCl2/醋酸反应则得到了少量的乙基5, 7-二氯-3-甲基吲哚-2-羧酸酯（36），这是通过在Fischer吲哚化反应中N-甲基基团的迁移形成的。

表征谱图