N-(p-tolyl)-2-(trichloromethyl)quinazolin-4-amine | 1177248-80-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-(p-tolyl)-2-(trichloromethyl)quinazolin-4-amine
• 英文别名: N-p-tolyl-2-(trichloromethyl)quinazolin-4-amine；N-(4-methylphenyl)-2-(trichloromethyl)quinazolin-4-amine
• CAS: 1177248-80-4
• 化学式: C₁₆H₁₂Cl₃N₃
• 分子量: 352.65
• InChiKey: VBKYYNSGKWVHQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-甲基-4(3H)-喹唑酮 在 4-二甲氨基吡啶 、 五氯化磷 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 2.33h， 生成 N-(p-tolyl)-2-(trichloromethyl)quinazolin-4-amine
  参考文献：
  名称：

  A new DMAP-catalyzed and microwave-assisted approach for introducing heteroarylamino substituents at position-4 of the quinazoline ring

  摘要：

  We report herein a new methodology for synthesizing quinazoline derivatives bearing a heteroarylamino moiety at position-4 of the quinazoline ring. As an alternative to the Buchwald-Hartwig cross-coupling reaction, which appears, until now, as the only efficient way to react 4-chloroquinazolines with numerous amino nitrogen-containing heterocycles displaying poor nucleophilicity, we developed a DMAP-catalyzed reaction involving microwave irradiation. Optimization of the reaction conditions led to the use of 30 mol % of DMAP in toluene, using a monomode microwave reactor and sealed vials. Moreover, the SNAr reaction intermediate salt was isolated and fully characterized. Finally, the procedure was extended to two different 2-substituted-quinazoline series and also to various anilines, demonstrating that this approach was a general efficient way to access to such 4-substituted quinazoline scaffolds of high pharmaceutical interest. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2014.09.024

文献信息

• A new DMAP-catalyzed and microwave-assisted approach for introducing heteroarylamino substituents at position-4 of the quinazoline ring
  作者：Armand Gellis、Charline Kieffer、Nicolas Primas、Gilles Lanzada、Michel Giorgi、Pierre Verhaeghe、Patrice Vanelle

  DOI：10.1016/j.tet.2014.09.024

  日期：2014.11

  We report herein a new methodology for synthesizing quinazoline derivatives bearing a heteroarylamino moiety at position-4 of the quinazoline ring. As an alternative to the Buchwald-Hartwig cross-coupling reaction, which appears, until now, as the only efficient way to react 4-chloroquinazolines with numerous amino nitrogen-containing heterocycles displaying poor nucleophilicity, we developed a DMAP-catalyzed reaction involving microwave irradiation. Optimization of the reaction conditions led to the use of 30 mol % of DMAP in toluene, using a monomode microwave reactor and sealed vials. Moreover, the SNAr reaction intermediate salt was isolated and fully characterized. Finally, the procedure was extended to two different 2-substituted-quinazoline series and also to various anilines, demonstrating that this approach was a general efficient way to access to such 4-substituted quinazoline scaffolds of high pharmaceutical interest. (C) 2014 Elsevier Ltd. All rights reserved.