4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-[3-(4-methylpiperazin-1-yl)propoxy]-3-quinolinecarbonitrile | 622369-06-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-[3-(4-methylpiperazin-1-yl)propoxy]-3-quinolinecarbonitrile
• 英文别名: 4-(2,4-Dichloro-5-methoxyanilino)-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile
• CAS: 622369-06-6
• 化学式: C₂₅H₂₇Cl₂N₅O₂
• 分子量: 500.428
• InChiKey: CIZNOHJXGBTGFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  73.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-(3-羟丙基)-4-甲基哌嗪 、 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-fluoro-3-quinolinecarbonitrile 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 以26%的产率得到4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-[3-(4-methylpiperazin-1-yl)propoxy]-3-quinolinecarbonitrile
  参考文献：
  名称：

  Facile preparation of new 4-phenylamino-3-quinolinecarbonitrile Src kinase inhibitors via 7-fluoro intermediates: Identification of potent 7-amino analogs

  摘要：

  A more efficient preparation of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (2), the penultimate intermediate in the synthesis of bosutinib (1a), was developed. New 7-alkoxy-4-phenylamino-3-quinolinecarbonitrile Src inhibitors were prepared from 5 and 9, the 6-ethoxy and 6-hydrogen analogs of 2. In addition, the fluoro group of 2 was readily displaced by primary and secondary amines to give 7-amino analogs. Two of these 7-amino analogs, 15 and 18, were potent Src inhibitors with in vivo activity. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.09.028

文献信息

• Facile preparation of new 4-phenylamino-3-quinolinecarbonitrile Src kinase inhibitors via 7-fluoro intermediates: Identification of potent 7-amino analogs
  作者：Diane H. Boschelli、Biqi Wu、Fei Ye、Haris Durutlic、Jennifer M. Golas、Judy Lucas、Frank Boschelli

  DOI：10.1016/j.bmc.2007.09.028

  日期：2008.1

  A more efficient preparation of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (2), the penultimate intermediate in the synthesis of bosutinib (1a), was developed. New 7-alkoxy-4-phenylamino-3-quinolinecarbonitrile Src inhibitors were prepared from 5 and 9, the 6-ethoxy and 6-hydrogen analogs of 2. In addition, the fluoro group of 2 was readily displaced by primary and secondary amines to give 7-amino analogs. Two of these 7-amino analogs, 15 and 18, were potent Src inhibitors with in vivo activity. (c) 2007 Elsevier Ltd. All rights reserved.