N-phenyl-2-(trichloromethyl)quinazolin-4-amine

• 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-phenyl-2-(trichloromethyl)quinazolin-4-amine
• 英文别名: N-phenyl-2-trichloromethylquinazolin-4-amine
• 化学式: C₁₅H₁₀Cl₃N₃
• 分子量: 338.623
• InChiKey: VQBNZVXRTHAMMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  21
• 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：
  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-phenyl-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 Copper-Catalyzed Synthesis of Functionalized Quinazolines from Isocyanides and Aniline Tri- and Dichloroacetonitrile Adducts through Intramolecular C–H Activation
  作者：Sayyed Tabatabai、Manijeh Nematpour、Elham Rezaee、Mehdi Jahani

  DOI：10.1055/s-0036-15588166

  日期：2017.7

  A novel class of substituted quinazolines were prepared in good yields by a one-pot three-component reaction of isocyanides with adducts of anilines and tri- or dichloroacetonitrile, followed by intramolecular C–H activation, catalyzed by copper(I) iodide with l -proline as a ligand in acetonitrile at room temperature.

  通过异氰化物与苯胺和三氯或二氯乙腈的加合物的一锅三组分反应，然后分子内 C-H 活化，由碘化铜（I）与 l-催化，以良好的收率制备了一类新型取代喹唑啉。脯氨酸在室温下作为乙腈中的配体。
• 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.