N-(4-nitrophenyl)-2-(trichloromethyl)quinazolin-4-amine | 1177248-68-8

• 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-(4-nitrophenyl)-2-(trichloromethyl)quinazolin-4-amine
• CAS: 1177248-68-8
• 化学式: C₁₅H₉Cl₃N₄O₂
• 分子量: 383.621
• InChiKey: XVSSIEJIFUCGOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  5

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-(4-nitrophenyl)-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

• Synthesis and in vitro antiplasmodial evaluation of 4-anilino-2-trichloromethylquinazolines
  作者：Pierre Verhaeghe、Nadine Azas、Sébastien Hutter、Caroline Castera-Ducros、Michèle Laget、Aurélien Dumètre、Monique Gasquet、Jean-Pierre Reboul、Sylvain Rault、Pascal Rathelot、Patrice Vanelle

  DOI：10.1016/j.bmc.2009.05.022

  日期：2009.7

  To identify a new safe antiplasmodial molecular scaffold, an original series of 2-trichloromethylquinazolines, functionalized in position 4 by an alkyl-or arylamino substituent, was synthesized from 4-chloro-2-trichloromethylquinazoline 1, via a cheap, fast and efficient solvent-free operating procedure. Among the 40 molecules prepared, several exhibit a good profile with both a significant antiplasmodial activity on the W2 Plasmodium falciparum strain (IC50 values: 0.4-2.2 mu M) and a promising toxicological behavior regarding human cells (HepG2/W2 selectivity indexes: 40-83), compared to the antimalarial drug compounds chloroquine and doxycycline. The in vitro antitoxoplasmic and antileishmanial evaluations were conducted in parallel on the most active molecules, showing that these ones specifically display antiplasmodial properties. (C) 2009 Elsevier Ltd. All rights reserved.
• 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.