4-Bromo-indole-1-carboxylic acid dimethylamide | 200418-18-4

• 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: 4-Bromo-indole-1-carboxylic acid dimethylamide
• 英文别名: 4-Bromo-N,N-dimethyl-1H-indole-1-carboxamide；4-bromo-N,N-dimethylindole-1-carboxamide
• CAS: 200418-18-4
• 化学式: C₁₁H₁₁BrN₂O
• 分子量: 267.125
• InChiKey: YDDWCVQBNHEPRD-UHFFFAOYSA-N

物化性质

• 沸点：
  358.8±34.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  25.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-Bromo-indole-1-carboxylic acid dimethylamide 在 N,N-二甲基丙烯基脲 、 三氯化铝 、 sodium bromide 作用下， 反应 6.75h， 生成 1-N,N-dimethylcarbamoyl-4-bromo-3-{4-[(1H-2-methylimidazo[4.5-c]pyrid-1-yl)methyl]benzoyl}indole
  参考文献：
  名称：

  Discovery and Evaluation of a Series of 3-Acylindole Imidazopyridine Platelet-Activating Factor Antagonists

  摘要：

  Studies conducted with the goal of discovering a second-generation platelet-activating factor (PAF) antagonist have identified a novel class of potent and orally active antagonists which have high aqueous solubility and long duration of action in animal models. The compounds arose from the combination of the lipophilic indole portion of Abbott's first-generation PAF antagonist ABT-299 (2) with the methylimidazopyridine heterocycle moiety of British Biotechnology's BB-882 (1) and possess the positive attributes of both of these clinical candidates. Structure-activity relationship (SAR) studies indicated that modification of the indole and benzoyl spacer of lead compound 7b gave analogues that were more potent, longer-lived, and bioavailable and resulted in the identification of 1-(N,N-dimethylcarbamoyl)-4-ethynyl-3-(3-fluoro-4-[(1H-2-methylimidazo[4,5-c]pyrid-1-yl)methyl] benzoyl}indole hydrochloride (ABT-491, 22m.HCl) which has been evaluated extensively and is currently in clinical development.

  DOI：

  10.1021/jm970389+
• 作为产物：
  描述：

  4-溴吲哚 、 二甲氨基甲酰氯 在 四丁基硫酸氢铵 、 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 生成 4-Bromo-indole-1-carboxylic acid dimethylamide
  参考文献：
  名称：

  光氧化还原催化通过连续的C–H和C–O键裂解引起的醚/醇双双烯丙基化

  摘要：

  为了容易获得对称的3，3′-二吲哚基甲烷衍生物，已经实现了吲哚衍生物与脂肪族醚或醇的可见光结合的2-位点选择性烷基化。实验数据表明，相继的光氧化还原催化诱导了自由基的加成和质子介导的Friedel-Crafts烷基化机理。

  DOI：

  10.1021/acs.orglett.7b03073

文献信息

• Rhodium-Catalyzed C2-Alkylation of Indoles with Cyclopropanols Using <i>N</i>,<i>N</i>-Dialkylcarbamoyl as a Traceless Directing Group
  作者：Kuppan Ramachandran、Pazhamalai Anbarasan

  DOI：10.1021/acs.orglett.2c02527

  日期：2022.9.23

  An efficient rhodium-catalyzed synthesis of C2-alkylated NH-free indoles has been achieved from substituted indoles and cyclopropanols. The reaction allows the synthesis of various C2-alkylated products in good to excellent yield. Important features of the method include the use of a N,N-dialkylcarbamoyl group as a traceless directing group, C–H/C–C bond functionalization, good functional group tolerance

  已经从取代的吲哚和环丙醇实现了有效的铑催化合成 C2-烷基化的无 NH 吲哚。该反应允许以良好至优异的产率合成各种 C2 烷基化产物。该方法的重要特点包括使用N，N-二烷基氨基甲酰基作为无痕导向基团，C-H/C-C键官能化，良好的官能团耐受性，适用范围广，可合成吡咯并[1,2- a ]吲哚，并鉴定潜在的中间体。
• 10.1039/d4ob00678j
  作者：Chen, Jia-Zhen、Wang, Zhong-Xia

  DOI：10.1039/d4ob00678j

  日期：——

  Indoles, indolines and hydronaphthylamines are ubiquitous structural motifs in natural products, pharmaceuticals, and biologically active molecules. In this paper, we report the synthesis of aminodihydronaphthyl-substituted indoles and indolines via a Ru-catalyzed carbamoyl-directed C–H functionalization of indoles and indolines with 7-azabenzonorbornadienes. In the presence of Cu(OAc)2 and AgSbF6

  吲哚、二氢吲哚和氢萘胺是天然产物、药物和生物活性分子中普遍存在的结构基序。在本文中，我们报道了通过Ru 催化的氨基甲酰基引导的吲哚和二氢吲哚与 7-氮杂苯降冰片二烯的 C-H 官能化合成氨基二氢萘基取代的吲哚和二氢吲哚。在 Cu(OAc) 2和 AgSbF 6存在下，[Ru( p-伞花烃)Cl 2 ] 2催化 1-氨基甲酰吲哚与 7-氮杂苯并降冰片二烯反应生成 2-(1-氨基-1,2-二氢萘- 2-基)吲哚。在相同条件下，1-氨基甲酰基二氢吲哚与7-氮杂苯并降冰片二烯反应得到7-(1-氨基-1,2-二氢萘-2-基)二氢吲哚。在这两种情况下，反应都会产生顺式构型的产物。
• J. Med. Chem. 1998, 41, 74-95
  作者：

  DOI：——

  日期：——
• Discovery and Evaluation of a Series of 3-Acylindole Imidazopyridine Platelet-Activating Factor Antagonists
  作者：Michael L. Curtin、Steven K. Davidsen、H. Robin Heyman、Robert B. Garland、George S. Sheppard、Alan S. Florjancic、Lianhong Xu、George M. Carrera、Douglas H. Steinman、Jeff A. Trautmann、Daniel H. Albert、Terrance J. Magoc、Paul Tapang、David A. Rhein、Richard G. Conway、Gongjin Luo、Jon F. Denissen、Kennan C. Marsh、Douglas W. Morgan、James B. Summers

  DOI：10.1021/jm970389+

  日期：1998.1.1

  Studies conducted with the goal of discovering a second-generation platelet-activating factor (PAF) antagonist have identified a novel class of potent and orally active antagonists which have high aqueous solubility and long duration of action in animal models. The compounds arose from the combination of the lipophilic indole portion of Abbott's first-generation PAF antagonist ABT-299 (2) with the methylimidazopyridine heterocycle moiety of British Biotechnology's BB-882 (1) and possess the positive attributes of both of these clinical candidates. Structure-activity relationship (SAR) studies indicated that modification of the indole and benzoyl spacer of lead compound 7b gave analogues that were more potent, longer-lived, and bioavailable and resulted in the identification of 1-(N,N-dimethylcarbamoyl)-4-ethynyl-3-(3-fluoro-4-[(1H-2-methylimidazo[4,5-c]pyrid-1-yl)methyl] benzoyl}indole hydrochloride (ABT-491, 22m.HCl) which has been evaluated extensively and is currently in clinical development.
• Photoredox Catalysis Induced Bisindolylation of Ethers/Alcohols via Sequential C–H and C–O Bond Cleavage
  作者：Lu Ye、Sai-Hu Cai、Ding-Xing Wang、Yi-Qiu Wang、Lin-Jie Lai、Chao Feng、Teck-Peng Loh

  DOI：10.1021/acs.orglett.7b03073

  日期：2017.11.17

  A visible-light-engaged 2-fold site-selective alkylation of indole derivatives with aliphatic ethers or alcohols has been accomplished for easy access to symmetric 3,3′-bisindolylmethane derivatives. The experimental data suggest a sequential photoredox catalysis induced radical addition and proton-mediated Friedel–Crafts alkylation mechanism.

  为了容易获得对称的3，3′-二吲哚基甲烷衍生物，已经实现了吲哚衍生物与脂肪族醚或醇的可见光结合的2-位点选择性烷基化。实验数据表明，相继的光氧化还原催化诱导了自由基的加成和质子介导的Friedel-Crafts烷基化机理。