4-chloro-N,N-dimethyl-1H-indole-1-carboxamide

• 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-chloro-N,N-dimethyl-1H-indole-1-carboxamide
• 英文别名: 4-Chloro-N,N-dimethyl-1H-indole-1-carboxamide；4-chloro-N,N-dimethylindole-1-carboxamide
• 化学式: C₁₁H₁₁ClN₂O
• 分子量: 222.674
• InChiKey: VSCVGVYAPKCAQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 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-chloro-N,N-dimethyl-1H-indole-1-carboxamide 在 platinum on activated charcoal 三氯化铝 、 sodium azide 、 水 、 氢气 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 25.0~60.0 ℃ 、405.3 kPa 条件下， 反应 42.25h， 生成
  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-氯吲哚 、 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-chloro-N,N-dimethyl-1H-indole-1-carboxamide
  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

• Regioselective C2 Oxidative Olefination of Indoles and Pyrroles through Cationic Rhodium(III)-Catalyzed CH Bond Activation
  作者：Bin Li、Jianfeng Ma、Weijia Xie、Haibin Song、Shansheng Xu、Baiquan Wang

  DOI：10.1002/chem.201301987

  日期：2013.9.2

  Be economic with your atoms! An efficient Rh‐catalyzed oxidative olefination of indoles and pyrroles with broad substrate scope and tolerance is reported (see scheme). The catalytic reaction proceeds with excellent regio‐ and stereoselectivity. The directing group N,N‐dimethylcarbamoyl was crucial for the reaction and could be removed easily.

  与您的原子经济！据报道，吲哚和吡咯的高效Rh催化氧化烯化反应具有广泛的底物范围和耐受性（参见方案）。催化反应以优异的区域选择性和立体选择性进行。N，N-二甲基氨基甲酰基导向基团对反应至关重要，可以很容易地除去。
• Ruthenium-Catalyzed Regioselective C2 Alkenylation of Indoles and Pyrroles via C–H Bond Functionalization
  作者：Bin Li、Jianfeng Ma、Weijia Xie、Haibin Song、Shansheng Xu、Baiquan Wang

  DOI：10.1021/jo401579m

  日期：2013.9.20

  An efficient ruthenium-catalyzed oxidative coupling of indoles and pyrroles with various alkenes at the C2-position assisted by employing the N,N-dimethylcarbamoyl moiety as a directing group is reported. The catalytic reaction proceeds in an excellent regio- and stereoselective manner.

  报道了通过使用N，N-二甲基氨基甲酰基部分作为导向基团辅助在C 2-位上的吲哚和吡咯与各种烯烃的有效的钌催化的氧化偶联。催化反应以极好的区域和立体选择性方式进行。
• Pd(<scp>ii</scp>)/Lewis acid catalyzed regioselective olefination of indole with dioxygen
  作者：Chen Tan、Hongwu Jiang、Miao Zeng、Kaiwen Li、Zhuqi Chen、Guochuan Yin

  DOI：10.1039/d2ob00006g

  日期：——

  through the pyrrolyl N-carboxamide group directed remote C–H activation at the C3 position of the indole with the Pd(II)/LA catalyst, whereas Pd(II) alone was a very sluggish catalyst under identical conditions. For the electron-deficient olefins, the directing N-carboxamide group was not essential for olefination with this Pd(II)/LA catalyst, demonstrating a different olefination pathway from that

  过渡金属离子通过 C-H 活化催化吲哚烯化是合成多功能生物活性乙烯基吲哚化合物的便捷方案；然而，在大多数情况下，化学计量的氧化剂是完成催化循环所必需的。本研究描述了以分子氧为唯一氧化剂的 Pd( II )/LA（LA：路易斯酸）催化吲哚烯化。与富电子烯烃的烯化反应通过吡咯基N-甲酰胺基团在 Pd( II )/LA 催化剂下在吲哚的 C3 位进行远程 C-H 活化而顺利进行，而单独的Pd( II ) 非常缓慢相同条件下的催化剂。对于缺电子烯烃，定向N使用这种 Pd( II )/LA 催化剂进行烯烃化时，α-甲酰胺基团不是必需的，这表明与富电子烯烃的烯烃化途径不同。值得注意的是，1 H NMR 动力学揭示了富电子烯烃的烯烃化反应比缺电子烯烃快得多。
• 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。
• 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.