2-methyl-N-(4-nitrophenyl)quinazolin-4-amine | 883732-62-5

• 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: 2-methyl-N-(4-nitrophenyl)quinazolin-4-amine
• CAS: 883732-62-5
• 化学式: C₁₅H₁₂N₄O₂
• 分子量: 280.286
• InChiKey: PKEXUAIIHVELRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 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：
  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 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 2.25h， 生成 2-methyl-N-(4-nitrophenyl)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 of Substituted Quinazolines: Application to the Synthesis of Verubulin
  作者：Jeffrey W. Lockman、Yevgeniya Klimova、Mark B. Anderson、J. Adam Willardsen

  DOI：10.1080/00397911.2010.529730

  日期：2012.6.15

  Through newly adapted methodology, 2-methyl-3H-quinazolin-4-one was activated using a number of methods followed by displacement to afford 4-aminoquinazolines. The most useful of these processes utilize the p-toluenesulfonate ester or I-2/PPh3 activation. Using this methodology, the anticancer vascular targeting clinical candidate verubulin (1) was synthesized in a highly efficient manner.
• 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.