(4-甲氧基苯基)(1-甲基-1H-苯并[d]咪唑-2-基)甲酮 | 85510-69-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (4-甲氧基苯基)(1-甲基-1H-苯并[d]咪唑-2-基)甲酮
• 英文名称: (4-methoxyphenyl)(1-methyl-1H-benzo[d]imidazol-2-yl)methanone
• 英文别名: 1-methyl-2-(4-methoxybenzoyl)benzimidazole；(4-Methoxyphenyl)-(1-methylbenzimidazol-2-yl)methanone
• CAS: 85510-69-6
• 化学式: C₁₆H₁₄N₂O₂
• 分子量: 266.299
• InChiKey: AXKFFRMTVGUAJS-UHFFFAOYSA-N

物化性质

• 沸点：
  471.4±47.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-甲氧基苯基)(1-甲基-1H-苯并[d]咪唑-2-基)甲酮 在 四(三苯基膦)钯 、 bis(η3-allyl-μ-chloropalladium(II)) 、 三溴化硼 、 potassium carbonate 、 caesium carbonate 作用下， 以 正己烷 、 二氯甲烷 、 二甲基亚砜 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 103.0h， 生成 1-(1-(2-(4-(1-methyl-1H-benzo[d]imidazole-2-carbonyl)phenoxy)nicotinoyl)piperidin-4-yl)ethanone
  参考文献：
  名称：

  Synthesis and in vitro characterization of cinnoline and benzimidazole analogues as phosphodiesterase 10A inhibitors

  摘要：

  Fifteen cinnoline analogues and six benzimidazole phosphodiesterase 10A (PDE10A) inhibitors were synthesized as potential PET radiopharmaceuticals and their in vitro activity as PDE10A inhibitors was determined. Nine out of twenty-one compounds were potent inhibitors of PDE10A with IC50 values ranging from 1.5 to 18.6 nM. Notably, the IC50 values of compounds 26a, 26b, and 33c were 1.52 +/- 0.18, 2.86 +/- 0.10, and 3.73 +/- 0.60 nM, respectively; these three compounds also showed high in vitro selectivity (> 1000-fold) for PDE10A over PDE 3A/3B, PDE4A/4B. The high potency and selectivity of these three compounds suggests that they could be radiolabeled with PET radionuclides for further evaluation of their in vivo pharmacological behavior and ability to quantify PDE10A in the brain. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.054
• 作为产物：
  描述：

  对甲氧基苯甲酰氯 在 sodium hydride 、 三乙胺 作用下， 以 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.75h， 生成 (4-甲氧基苯基)(1-甲基-1H-苯并[d]咪唑-2-基)甲酮
  参考文献：
  名称：

  Synthesis and in vitro characterization of cinnoline and benzimidazole analogues as phosphodiesterase 10A inhibitors

  摘要：

  Fifteen cinnoline analogues and six benzimidazole phosphodiesterase 10A (PDE10A) inhibitors were synthesized as potential PET radiopharmaceuticals and their in vitro activity as PDE10A inhibitors was determined. Nine out of twenty-one compounds were potent inhibitors of PDE10A with IC50 values ranging from 1.5 to 18.6 nM. Notably, the IC50 values of compounds 26a, 26b, and 33c were 1.52 +/- 0.18, 2.86 +/- 0.10, and 3.73 +/- 0.60 nM, respectively; these three compounds also showed high in vitro selectivity (> 1000-fold) for PDE10A over PDE 3A/3B, PDE4A/4B. The high potency and selectivity of these three compounds suggests that they could be radiolabeled with PET radionuclides for further evaluation of their in vivo pharmacological behavior and ability to quantify PDE10A in the brain. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.054

文献信息

• Palladium catalyzed carbonylative generation of potent, pyridine-based acylating electrophiles for the functionalization of arenes to ketones
  作者：Yi Liu、Angela M. Kaiser、Bruce A. Arndtsen

  DOI：10.1039/d0sc03129a

  日期：——

  ultimate elimination of a new class of potent Friedel–Crafts acylating agent: N-acyl pyridinium salts. The latter can be exploited to modulate reactivity and selectivity in carbonylative arene functionalization chemistry, and allow the efficient synthesis of ketones with a diverse array of (hetero)arenes.

  我们在这里描述了钯催化路线的设计，该路线通过（杂）芳烃与芳基或乙烯基三氟甲磺酸酯的羰基化偶联生成芳基酮。在这种情况下，在钯上使用大咬角的Xantphos配体提供了一条独特的途径，可以平衡相对较强的C（sp 2）-OTf键的活化与最终消除新型强力Friedel-Crafts酰化剂：N-酰基吡啶鎓盐。可以利用后者来调节羰基芳烃官能化化学中的反应性和选择性，并允许有效地合成具有多种（杂）芳烃的酮。
• Palladium-Catalyzed Carbonylative CH Activation of Heteroarenes
  作者：Xiao-Feng Wu、Pazhamalai Anbarasan、Helfried Neumann、Matthias Beller

  DOI：10.1002/anie.201003895

  日期：——

  Not only carbonylation: The first carbonylative cross‐coupling reactions towards ketones using CH activation have been developed. Various heteroarenes, such as oxazoles, thiazoles, and imidazoles were used as coupling partners in this methodology. DBU=1,8‐diazabicyclo[5.4.0]undec‐7‐ene, dppp=1,3‐bisdiphenylphosphinopropane, DMF=N,N‐dimethylformamide.

  不仅羰基化：已经开发出使用CH活化作用与酮进行的首个羰基交叉偶联反应。在该方法中，各种杂芳基化合物，例如恶唑，噻唑和咪唑被用作偶联伴侣。DBU ＝ 1，8-二氮杂双环[5.4.0]十一月-7-烯，dppp ＝ 1，3-双二苯基膦基丙烷，DMF ＝N，N-二甲基甲酰胺。
• An Electrophilic Approach to the Palladium-Catalyzed Carbonylative C–H Functionalization of Heterocycles
  作者：Jevgenijs Tjutrins、Bruce A. Arndtsen

  DOI：10.1021/jacs.5b07098

  日期：2015.9.23

  highly electrophilic intermediates. Overall, this provides with an atom-economical and general synthetic route to generate aryl-(hetero)aryl ketones using stable reagents (aryl iodides and CO) and without the typical need to exploit pre-metalated heterocycles in carbonylative coupling chemistry.

  描述了一种钯催化的分子间羰基化 CH 官能化方法。这种转化由 P(t)Bu3 配位的钯催化剂介导，并允许衍生化各种杂环，包括吡咯、吲哚、咪唑、苯并恶唑和呋喃。初步研究表明，该反应可能通过催化形成高度亲电子中间体来进行。总体而言，这提供了使用稳定试剂（芳基碘化物和 CO）生成芳基-（杂）芳基酮的原子经济和通用合成路线，并且通常不需要在羰基化偶联化学中利用预金属化杂环。
• Palladium-Catalyzed Chlorocarbonylation of C(sp²)-Triflates as a Route to Heteroarene C–H Functionalization and Ketone Synthesis
  作者：Yi Liu、Bruce A. Arndtsen

  DOI：10.1021/acs.organomet.2c00479

  日期：2022.11.14

  N-heterocycles to generate ketones using a Pd/Xantphos catalyst in concert with LiCl is described. Mechanistic studies suggest the synergistic influence of the large-bite-angle phosphine on palladium with chloride allows the reductive elimination of a reactive acid chloride intermediate for subsequent reaction with heterocycles. Together, this offers a convergent approach to ketones with minimal waste from

  描述了使用 Pd/Xantphos 催化剂与 LiCl 配合使用 N-杂环的羰基化 C-H 官能化生成酮。机理研究表明，大咬角膦对钯与氯化物的协同影响允许还原消除反应性酰氯中间体，以便随后与杂环反应。总之，这为酮类提供了一种聚合方法，可最大限度地减少可用底物的浪费：芳基或乙烯基三氟甲磺酸酯、CO 和 N-杂芳烃。
• Nucleophilic acylation of benzimidazole
  作者：B. I. Khristich、A. M. Simonov、E. N. Shepelenko、V. A. Yatsimirskii

  DOI：10.1007/bf00512823

  日期：1983.1