2-chloro-1,5,6-trimethyl-1H-benzo[d]imidazole | 39791-97-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-chloro-1,5,6-trimethyl-1H-benzo[d]imidazole
• 英文别名: 2-Chloro-1,5,6-trimethylbenzimidazole
• CAS: 39791-97-4
• 化学式: C₁₀H₁₁ClN₂
• 分子量: 194.664
• InChiKey: ZQNHOCWHDDHEMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-chloro-1,5,6-trimethyl-1H-benzo[d]imidazole 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 1,5,6-trimethyl-N-(piperidin-4-yl)-1H-benzo[d]imidazol-2-amine
  参考文献：
  名称：

  Novel 3-Trifluoromethyl-1,2,4-oxadiazole Analogues of Astemizole with Multi-stage Antiplasmodium Activity and In Vivo Efficacy in a Plasmodium berghei Mouse Malaria Infection Model

  摘要：

  DOI：

  10.1021/acs.jmedchem.2c01516
• 作为产物：
  描述：

  4，5-二甲基-1，2-苯二胺 在 sodium hydride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三氯氧磷 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-chloro-1,5,6-trimethyl-1H-benzo[d]imidazole
  参考文献：
  名称：

  4-(2-Pyridyl)piperazine-1-benzimidazoles as potent TRPV1 antagonists

  摘要：

  A series of 4-(2-pyridyl)piperazine-1-benzimidazole analogues based on compound I was synthesized and evaluated for TRPV1 antagonist activity in capsaicin-induced (CAP) and pH5.5-induced (pH) FLIPR assays in a human TRPV1 -expressing HEK293 cell line. Potent TRPV1 antagonists were identified through SAR studies. From these studies, several antagonists were found, with IC50 values ranging from 32nM to similar to5000nM. Among these, 11 [IC50 = 90nM (CAP) and 104nM (pH)] was further evaluated and found to be orally available in rats (F% = 19.7). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.11.021

文献信息

• Transition‐Metal‐Free Base‐Controlled C−N Coupling Reactions: Selective Mono<i>Versus</i>Diarylation of Primary Amines with 2‐Chlorobenzimidazoles
  作者：Wei Sang、Yan‐Yan Gong、Hua Cheng、Rui Zhang、Ye Yuan、Guang‐Gao Fan、Zhi‐Qin Wang、Cheng Chen、Francis Verpoort

  DOI：10.1002/adsc.202001365

  日期：2021.3.2

  Herein, a base‐controlled protocol was developed for the C−N coupling of primary amines and 2‐chlorobenzimidazoles, affording a handful of secondary or tertiary amines in a selective fashion. Moreover, this protocol was realized under transition‐metal‐free conditions, and the variation of the base from iPr2NH to LiOtBu completely switched the selectivity from monoarylation to diarylation. Further investigations

  本文中，开发了一种碱控制的方案，用于伯胺和2-氯苯并咪唑的C-N偶联，以选择性方式提供了少量仲胺或叔胺。此外，该方案是在无过渡金属条件下实现的，碱从i Pr 2 NH到LiO t Bu的变化完全将选择性从单芳基化转变为二芳基化。进一步的研究表明，所用碱的种类，内在的碱性和数量极大地影响了这些反应。
• Palladium‐Catalyzed Ligand‐Free C‐N Coupling Reactions: Selective Diheteroarylation of Amines with 2‐Halobenzimidazoles
  作者：Wei Sang、Ayao Jean Gavi、Bao‐Yi Yu、Hua Cheng、Ye Yuan、Yuan Wu、Petra Lommens、Cheng Chen、Francis Verpoort

  DOI：10.1002/asia.201901465

  日期：2020.1.2

  examples were reported for the di-substituted products and the selectivity of mono- vs. di-substitution was relatively low. Considering the potential values of the di-substituted products, we accomplished the first selective diheteroarylation of amines with 2-halobenzimidazoles. Notably, this Pd-catalyzed transformation was realized under ligand-free conditions. Accordingly, numerous target products

  2-氨基苯并咪唑广泛存在于许多生物活性分子中。通常，这些分子的制备可以通过将2-卤代苯并咪唑与胺单取代来实现。然而，报道了关于二取代产物的罕见实例，并且单取代与二取代的选择性相对较低。考虑到二取代产物的潜在价值，我们完成了胺与2-卤代苯并咪唑的首次选择性二杂芳基化反应。值得注意的是，这种钯催化的转化是在无配体条件下实现的。因此，从各种芳族或脂族胺和2-卤代苯并咪唑有效地生产了许多目标产物。值得注意的是，X射线晶体学进一步证实了两种代表性产品。更重要的是
• 4-(2-Pyridyl)piperazine-1-benzimidazoles as potent TRPV1 antagonists
  作者：Bin Shao、Jincheng Huang、Qun Sun、Kenneth J. Valenzano、Lori Schmid、Scott Nolan

  DOI：10.1016/j.bmcl.2004.11.021

  日期：2005.2

  A series of 4-(2-pyridyl)piperazine-1-benzimidazole analogues based on compound I was synthesized and evaluated for TRPV1 antagonist activity in capsaicin-induced (CAP) and pH5.5-induced (pH) FLIPR assays in a human TRPV1 -expressing HEK293 cell line. Potent TRPV1 antagonists were identified through SAR studies. From these studies, several antagonists were found, with IC50 values ranging from 32nM to similar to5000nM. Among these, 11 [IC50 = 90nM (CAP) and 104nM (pH)] was further evaluated and found to be orally available in rats (F% = 19.7). (C) 2004 Elsevier Ltd. All rights reserved.
• Novel 3-Trifluoromethyl-1,2,4-oxadiazole Analogues of Astemizole with Multi-stage Antiplasmodium Activity and <i>In Vivo</i> Efficacy in a <i>Plasmodium berghei</i> Mouse Malaria Infection Model
  作者：Dickson Mambwe、Constance M. Korkor、Amanda Mabhula、Zama Ngqumba、Cleavon Cloete、Malkeet Kumar、Paula Ladeia Barros、Meta Leshabane、Dina Coertzen、Dale Taylor、Liezl Gibhard、Mathew Njoroge、Nina Lawrence、Janette Reader、Diogo Rodrigo Moreira、Lyn-Marie Birkholtz、Sergio Wittlin、Timothy J. Egan、Kelly Chibale

  DOI：10.1021/acs.jmedchem.2c01516

  日期：2022.12.22