3-(benzyloxy)-5-(4-methoxyphenyl)-2-(4-methylphenyl)pyrazine | 1410165-27-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-(benzyloxy)-5-(4-methoxyphenyl)-2-(4-methylphenyl)pyrazine
• CAS: 1410165-27-3
• 化学式: C₂₅H₂₂N₂O₂
• 分子量: 382.462
• InChiKey: LLHLUOZVFNZYGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.71
• 重原子数：
  29.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  44.24
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-(benzyloxy)-5-(4-methoxyphenyl)-2-(4-methylphenyl)pyrazine 在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以98%的产率得到6-(4-methoxyphenyl)-3-(4-methylphenyl)-1H-pyrazin-2-one
  参考文献：
  名称：

  Design and synthesis of 2(1H)-pyrazinones as inhibitors of protein kinases

  摘要：

  Kinase enzymes play a key role in the development and progression of cancer. Inhibitors of deregulated kinases are effective small molecule anticancer drugs. The 2(1H)-pyrazinone heterocycle is a previously unexploited motif that can fulfil the structural requirements for ATP-competitive inhibition of kinases. Rapid solution-phase syntheses of novel 3,5- and 3,6-disubstituted-2(1H)-pyrazinones were developed through selective, sequential substitution of 2,5-dihalo-3-benzyloxypyrazine and 3,5-dihalo-2(1H)-pyrazinone intermediates. Palladium-catalysed cross-couplings and SNAr reactions were used to introduce substituents chosen on the basis of the calculated physicochemical properties of the target pyrazinones. Representative compounds demonstrated good solubility, kinase inhibitory activity and antiproliferative activity in human tumour cells, confirming the suitability of this chemical class as a kinase-focused library. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2012.09.039
• 作为产物：
  描述：

  3-(benzyloxy)-5-bromo-2-chloropyrazine 在 bis-triphenylphosphine-palladium(II) chloride 、 [2-[(dimethylamino-kN)methyl]phenyl-kC](tricyclohexylphosphine)(trifluoroacetato-kO)-palladium 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 、 乙腈 为溶剂， 反应 16.33h， 生成 3-(benzyloxy)-5-(4-methoxyphenyl)-2-(4-methylphenyl)pyrazine
  参考文献：
  名称：

  Design and synthesis of 2(1H)-pyrazinones as inhibitors of protein kinases

  摘要：

  Kinase enzymes play a key role in the development and progression of cancer. Inhibitors of deregulated kinases are effective small molecule anticancer drugs. The 2(1H)-pyrazinone heterocycle is a previously unexploited motif that can fulfil the structural requirements for ATP-competitive inhibition of kinases. Rapid solution-phase syntheses of novel 3,5- and 3,6-disubstituted-2(1H)-pyrazinones were developed through selective, sequential substitution of 2,5-dihalo-3-benzyloxypyrazine and 3,5-dihalo-2(1H)-pyrazinone intermediates. Palladium-catalysed cross-couplings and SNAr reactions were used to introduce substituents chosen on the basis of the calculated physicochemical properties of the target pyrazinones. Representative compounds demonstrated good solubility, kinase inhibitory activity and antiproliferative activity in human tumour cells, confirming the suitability of this chemical class as a kinase-focused library. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2012.09.039