Ethyl 5,7-Dichloro-1-methylindole-2-carboxylate | 108797-30-4

• 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 5,7-Dichloro-1-methylindole-2-carboxylate
• 英文别名: ethyl 5,7-dichloro-1-methyl-1H-indole-2-carboxylate
• CAS: 108797-30-4
• 化学式: C₁₂H₁₁Cl₂NO₂
• 分子量: 272.131
• InChiKey: MZJOEQGEUAHMGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  17
• 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 5,7-Dichloro-1-methylindole-2-carboxylate 在 三乙基硅烷 、 三甲基铝 作用下， 以 三氟乙酸 为溶剂， 反应 3.75h， 生成 5,7-Dichloro-2-(4,5-dihydro-1H-imidazol-2-yl)-1-methyl-2,3-dihydro-1H-indole
  参考文献：
  名称：

  .alpha.2-Adrenergic agonists/antagonists: the synthesis and structure-activity relationships of a series of indolin-2-yl and tetrahydroquinolin-2-yl imidazolines

  摘要：

  The synthesis and alpha 2-adrenergic activity of a series of indolin-2-yl and tetrahydroquinolin-2-yl imidazolines are described. The indolin-2-yl imidazoline 4b was found to possess potent alpha 2-adrenergic agonist and antagonist activity. The modification of the substituents on the indoline ring of 4b has led to the separation of these activities. Substitution on the aromatic ring of 4b with halogen or increasing the size of the N-alkyl substituent of 4b gave alpha 2-adrenergic antagonists without agonist activity. The N-allylindoline 4d is more potent than idazoxan in vitro and is equipotent in vivo, but is less receptor selective (alpha 2 vs. alpha 1) than idazoxan. The cis-1,3-dimethylindolin-2-yl imidazoline 6a is an alpha 2-adrenergic agonist equal in potency to clonidine in vitro, while the trans-1,3-dimethylindolin-2-yl imidazoline 6b is a moderately potent alpha 2-adrenergic antagonist.

  DOI：

  10.1021/jm00392a005
• 作为产物：
  描述：

  5,7-二氯-1H-吲哚-2-甲酸乙酯 、 硫酸二甲酯 在 氢氧化钾 作用下， 以 丙酮 为溶剂， 以64.3%的产率得到Ethyl 5,7-Dichloro-1-methylindole-2-carboxylate
  参考文献：
  名称：

  Abnormal Fischer indolization and its related compounds. XXII. Fischer indolization of ethyl pyruvate 2-(2-chloro- and 2,6-dichlorophenyl)methylhydrazones.

  摘要：

  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。

  DOI：

  10.1248/cpb.38.597

文献信息

• Synthesis of Pyridazino[4,5‐<i>b</i>]indoles by [3+3] Annulation of 2‐Alkenylindoles and Hydrazonyl Chlorides
  作者：Shuting Zhang、Xinyu Zhang、Lesong Li、Zhenyu Shi、Yang Wang

  DOI：10.1002/chem.202400278

  日期：——

  A environmentally benign and efficient method for the synthesis of pyridazino[4,5-b]indoles has been developed via a novel [3+3] annulation reaction of 2-alkenylindoles and hydrazonyl chlorides. This reaction proceeded smoothly in the presence of base with excellent yield and a broad substrate scope.

  通过2-烯基吲哚和腙氯的新型[3+3]环化反应，开发了一种环境友好且高效的哒嗪并[4,5- b ]吲哚合成方法。该反应在碱存在下顺利进行，产率优异，底物范围广泛。
• ISHII, HISASHI;MURAKAMI, YASUOKI;ISHIKAWA, TSUTOMU, CHEM. AND PHARM. BULL. , 38,(1990) N, C. 597-604
  作者：ISHII, HISASHI、MURAKAMI, YASUOKI、ISHIKAWA, TSUTOMU

  DOI：——

  日期：——
• HLASTA, DENNIS J.;LUTTINGER, DANIEL;PERRONE, MARK H.;SILBERNAGEL, MARLA J+, J. MED. CHEM., 30,(1987) N 9, 1555-1562
  作者：HLASTA, DENNIS J.、LUTTINGER, DANIEL、PERRONE, MARK H.、SILBERNAGEL, MARLA J+

  DOI：——

  日期：——
• .alpha.2-Adrenergic agonists/antagonists: the synthesis and structure-activity relationships of a series of indolin-2-yl and tetrahydroquinolin-2-yl imidazolines
  作者：Dennis J. Hlasta、Daniel Luttinger、Mark H. Perrone、Marla J. Silbernagel、Susan J. Ward、Dean R. Haubrich

  DOI：10.1021/jm00392a005

  日期：1987.9

  The synthesis and alpha 2-adrenergic activity of a series of indolin-2-yl and tetrahydroquinolin-2-yl imidazolines are described. The indolin-2-yl imidazoline 4b was found to possess potent alpha 2-adrenergic agonist and antagonist activity. The modification of the substituents on the indoline ring of 4b has led to the separation of these activities. Substitution on the aromatic ring of 4b with halogen or increasing the size of the N-alkyl substituent of 4b gave alpha 2-adrenergic antagonists without agonist activity. The N-allylindoline 4d is more potent than idazoxan in vitro and is equipotent in vivo, but is less receptor selective (alpha 2 vs. alpha 1) than idazoxan. The cis-1,3-dimethylindolin-2-yl imidazoline 6a is an alpha 2-adrenergic agonist equal in potency to clonidine in vitro, while the trans-1,3-dimethylindolin-2-yl imidazoline 6b is a moderately potent alpha 2-adrenergic antagonist.
• 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。