2-amino-4-chloro-1H-indole-3-carbonitrile

• 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: 2-amino-4-chloro-1H-indole-3-carbonitrile
• 化学式: C₉H₆ClN₃
• 分子量: 191.62
• InChiKey: KGPJFHKYONXINN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  65.6
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  α-溴代肉桂醛 、 2-amino-4-chloro-1H-indole-3-carbonitrile 在 (S)-5-benzyl-2-(perfluorophenyl)-6,8-dihydro-5H-[1,2,4]triazolo[3,4-c][1,4]oxazin-2-ium tetrafluoroborate 、 potassium carbonate 作用下， 以 1,2-二氯乙烷 为溶剂， 以98%的产率得到
  参考文献：
  名称：

  N-杂环卡宾催化 2-氨基-1H-吲哚和溴烯醛的对映选择性环化用于合成手性 2-芳基-2,3-二氢嘧啶基[1,2-a]吲哚-4 (1H)-酮

  摘要：

  开发了一种高效的 N-杂环卡宾 (NHC) 催化的 2-溴烯醛与 2-氨基-1 H-吲哚的对映选择性 [3 + 3] 成环反应。使用NHCs作为催化剂合成了一系列功能化的2-芳基-2,3-二氢嘧啶基[1,2- a ]吲哚-4(1H ) -酮，收率良好，具有高至优异的对映选择性。

  DOI：

  10.1039/d3ob01006f
• 作为产物：
  描述：

  2,3-二氯硝基苯 在 sodium hydride 、 溶剂黄146 、 锌 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.75h， 生成 2-amino-4-chloro-1H-indole-3-carbonitrile
  参考文献：
  名称：

  Synthesis and evaluation of 5-(arylthio)-9 H -pyrimido[4,5- b ]indole-2,4-diamines as receptor tyrosine kinase and thymidylate synthase inhibitors and as antitumor agents

  摘要：

  In an effort to optimize the structural requirements for combined cytostatic and cytotoxic effects in single agents, a series of 5-(arylthio)-9H-pyrimido[4,5-b]indole-2,4-diamines 3-7 were synthesized and evaluated as inhibitors of receptor tyrosine kinases (RTKs) as well as thymidylate synthase (TS). The synthesis of these compounds involved the nucleophilic displacement of the common intermediate 5-bromo/5-chloro-9H-pyrimido[4,5-b]indole-2,4-diamine with appropriate aryl thiols. A novel four step synthetic scheme to the common intermediate was developed which is more efficient relative to the previously reported six-step sequence. Biological evaluation of these compounds indicated dual activity in RTKs and human TS (hTS). In the VEGFR-2 assay, compound 5 was equipotent to the standard compound semaxanib and was better than standard TS inhibitor pemetrexed, in the hTS assay. Compounds 3, 6 and 7 were nanomolar inhibitors of hTS and were several fold better than pemetrexed. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.02.018

文献信息

• Synthesis and evaluation of 5-(arylthio)-9 H -pyrimido[4,5- b ]indole-2,4-diamines as receptor tyrosine kinase and thymidylate synthase inhibitors and as antitumor agents
  作者：Nilesh Zaware、Roy Kisliuk、Anja Bastian、Michael A. Ihnat、Aleem Gangjee

  DOI：10.1016/j.bmcl.2017.02.018

  日期：2017.4

  In an effort to optimize the structural requirements for combined cytostatic and cytotoxic effects in single agents, a series of 5-(arylthio)-9H-pyrimido[4,5-b]indole-2,4-diamines 3-7 were synthesized and evaluated as inhibitors of receptor tyrosine kinases (RTKs) as well as thymidylate synthase (TS). The synthesis of these compounds involved the nucleophilic displacement of the common intermediate 5-bromo/5-chloro-9H-pyrimido[4,5-b]indole-2,4-diamine with appropriate aryl thiols. A novel four step synthetic scheme to the common intermediate was developed which is more efficient relative to the previously reported six-step sequence. Biological evaluation of these compounds indicated dual activity in RTKs and human TS (hTS). In the VEGFR-2 assay, compound 5 was equipotent to the standard compound semaxanib and was better than standard TS inhibitor pemetrexed, in the hTS assay. Compounds 3, 6 and 7 were nanomolar inhibitors of hTS and were several fold better than pemetrexed. (C) 2017 Elsevier Ltd. All rights reserved.
• N-Heterocyclic carbene-catalyzed enantioselective annulation of 2-amino-1<i>H</i>-indoles and bromoenals for the synthesis of chiral 2-aryl-2,3-dihydropyrimido[1,2-<i>a</i>]indol-4 (1<i>H</i>)-ones
  作者：Jianbo Zhao、Min Wu、Jiamin Luo、Lei Shi、Hao Li

  DOI：10.1039/d3ob01006f

  日期：——

  N-heterocyclic carbene (NHC)-catalyzed enantioselective [3 + 3] annulation of 2-bromoenals with 2-amino-1H-indoles has been developed. A series of functionalized 2-aryl-2,3-dihydropyrimido[1,2-a]indol-4(1H)-ones were synthesized using NHCs as the catalyst in good yields with high to excellent enantioselectivities.

  开发了一种高效的 N-杂环卡宾 (NHC) 催化的 2-溴烯醛与 2-氨基-1 H-吲哚的对映选择性 [3 + 3] 成环反应。使用NHCs作为催化剂合成了一系列功能化的2-芳基-2,3-二氢嘧啶基[1,2- a ]吲哚-4(1H ) -酮，收率良好，具有高至优异的对映选择性。