3-(吗啉-4-基甲基)-2-苯基咪唑并[1,2-a]吡啶 | 3323-03-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-(吗啉-4-基甲基)-2-苯基咪唑并[1,2-a]吡啶
• 英文名称: 4-((2-phenylimidazo[1,2-a]pyridin-3-yl)methyl)morpholine
• 英文别名: Imidazo(1,2-a)pyridine, 3-(morpholinomethyl)-2-phenyl-；4-[(2-phenylimidazo[1,2-a]pyridin-3-yl)methyl]morpholine
• CAS: 3323-03-3
• 化学式: C₁₈H₁₉N₃O
• 分子量: 293.368
• InChiKey: IXMAJNIDZSUZTI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  29.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为产物：
  描述：

  alpha-氯乙酰苯 在 聚合甲醛 、 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 生成 3-(吗啉-4-基甲基)-2-苯基咪唑并[1,2-a]吡啶
  参考文献：
  名称：

  Discovery of new leads against Mycobacterium tuberculosis using scaffold hopping and shape based similarity

  摘要：

  BM212 [1,5-diaryl-2-methyl-3-(4-methylpiperazin-1-yl)-methyl-pyrrole] is a pyrrole derivative with strong inhibitory activity against drug resistant Mycobacterium tuberculosis and mycobacteria residing in macrophages. However, it was not pursued because of its poor pharmacokinetics and toxicity profile. Our goal was to design and synthesize new antimycobacterial BM212 analogs with lower toxicity and better pharmacokinetic profile. Using the scaffold hopping approach, three structurally diverse heterocycles - 2,3-disubstituted imidazopyridines, 2,3-disubstituted benzimidazoles and 1,2,4-trisubstituted imidazoles emerged as promising antitubercular agents. All compounds were synthesized through easy and convenient methods and their structures confirmed by IR, H-1 NMR, C-11 NMR and MS. In-vitro cytotoxicity studies on normal kidney monkey cell lines and HepG2 cell lines, as well as metabolic stability studies on rat liver microsomes for some of the most active compounds, established that these compounds have negligible cytotoxicity and are metabolically stable. Interestingly the benzimidazole compound (4a) is as potent as the parent molecule BM212 (MIC 2.3 mu g/ml vs 0.7-1.5 mu g/ml), but is devoid of the toxicity against HepG2 cell lines (IC50 203.10 mu M vs 7.8 mu M). (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.07.034

文献信息

• Four-component synthesis of 3-aminomethylated imidazoheterocycles in EtOH under catalyst-free, oxidant-free and mild conditions
  作者：Qing-Wen Gui、Bin-Bin Wang、Sha Zhu、Fu-Long Li、Meng-Xue Zhu、Min Yi、Jia-Ling Yu、Zhi-Lin Wu、Wei-Min He

  DOI：10.1039/d1gc01017d

  日期：——

  With green ethanol as the sole solvent, various 3-aminomethylated imidazoheterocycles were efficiently synthesized in one step through a four-component reaction of equimolar cheap and commercially available reactants at ambient temperature under metal-free, oxidant-free and mild conditions.

  以绿色乙醇为唯一溶剂，在环境温度，无金属，无氧化剂和温和的条件下，通过等摩尔廉价且可商购的反应物的四组分反应，一步有效地合成了各种3-氨基甲基化的咪唑杂环。
• Use of Imidazo[1,2‐ <i>a</i> ]pyridine as a Carbonyl Surrogate in a Mannich‐Like, Catalyst Free, One‐Pot Reaction
  作者：Gunaganti Naresh、Naga Rajiv Lakkaniga、Anupreet Kharbanda、Wei Yan、Brendan Frett、Hong‐yu Li

  DOI：10.1002/ejoc.201801430

  日期：2019.1.31

  developed a simple and efficient protocol to aminomethylate the C‐3 position of imidazo[1,2‐a]pyridine through a multicomponent, decarboxylation reaction involving imidazo[1,2‐a]pyridine, a secondary amine, and glyoxylic acid. The developed protocol requires mild reaction conditions and furnishes diverse imidazo[1,2‐a]pyridine analogues from commercially available starting materials.

  我们开发了一种简单而有效的协议来aminomethylate咪唑并[1,2的C-3位一个通过多组分]吡啶，脱羧反应涉及咪唑并[1,2一]吡啶，仲胺，和二羟乙酸。制定的方案要求反应条件温和，并从市售起始原料中提供多种咪唑并[1,2- a ]吡啶类似物。
• Oxidative Cross-Coupling of sp³- and sp²-Hybridized C–H Bonds: Vanadium-Catalyzed Aminomethylation of Imidazo[1,2-<i>a</i>]pyridines
  作者：Pinku Kaswan、Ashley Porter、Kasiviswanadharaju Pericherla、Marissa Simone、Sean Peters、Anil Kumar、Brenton DeBoef

  DOI：10.1021/acs.orglett.5b02539

  日期：2015.11.6

  The vanadium-catalyzed oxidative coupling of substituted 2-arylimidiazo[1,2-a]pyridines to N-methylmorpholine oxide, which acts as both a coupling partner and an oxidant, has been achieved. This reaction was applied to various substituted imidiazo[1,2-a]pyridine and indole substrates, resulting in yields as high as 90%. Mechanistic investigations indicate that the reaction may proceed via a Mannich-type

  已经实现了取代的2-芳基咪唑并[1,2- a ]吡啶对N-甲基吗啉氧化物的钒催化氧化偶联，N-甲基吗啉既是偶联剂又是氧化剂。该反应用于各种取代的咪唑并[1,2- a ]吡啶和吲哚底物，产率高达90％。机理研究表明该反应可以通过曼尼希型过程进行。这项工作证明了如何将氧化氨基甲基化用作将叔胺引入杂环的有用方法，从而为常规曼尼希型反应提供了另一种方法。
• Aminomethylation of Imidazoheterocycles with Morpholine
  作者：Susmita Mondal、Sadhanendu Samanta、Mukta Singsardar、Alakananda Hajra

  DOI：10.1021/acs.orglett.7b01594

  日期：2017.7.21

  hitherto unreported aminomethylation occurs at C-3 of imidazopyridines with morpholine in the presence of (diacetoxyiodo)benzene at ambient temperature in short reaction times. This methodology is also applicable to indolizine, imidazo[2,1-b]thiazole, benzo[d]imidazo[2,1-b]thiazole, and indole. Interestingly, the aminomethylation involving morpholine as a source of methylene group is a new phenomenon. This

  在（二乙酰氧基碘）苯的存在下，在环境温度下以短的反应时间，在吗啉对咪唑并吡啶的C-3处发生了迄今未报道的氨基甲基化。该方法也适用于吲哚嗪，咪唑并[2,1- b ]噻唑，苯并[ d ]咪唑并[2,1- b ]噻唑和吲哚。有趣的是，涉及吗啉作为亚甲基来源的氨基甲基化是一种新现象。该方案对于在温和的反应条件下合成氨基甲基化衍生物具有很大的潜力。
• Derivatives of Imidazole. I. Synthesis and Reactions of Imidazo[1,2-α]pyridines with Analgesic, Antiinflammatory, Antipyretic, and Anticonvulsant Activity
  作者：Luigi Almirante、Luigi Polo、Alfonso Mugnaini、Ercolina Provinciali、Pierluigi Rugarli、Adriana Biancotti、Afro Gamba、Walter Murmann

  DOI：10.1021/jm00327a007

  日期：1965.5