N-(4,6-dichloropyrimidin-2-yl)-N-((3-isopropylisoxazol-5-yl)methyl)acetamide | 1449314-08-2

• 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: N-(4,6-dichloropyrimidin-2-yl)-N-((3-isopropylisoxazol-5-yl)methyl)acetamide
• 英文别名: N-(4,6-dichloropyrimidin-2-yl)-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]acetamide
• CAS: 1449314-08-2
• 化学式: C₁₃H₁₄Cl₂N₄O₂
• 分子量: 329.186
• InChiKey: YNJNCBPERJVHFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(4,6-dichloropyrimidin-2-yl)-N-((3-isopropylisoxazol-5-yl)methyl)acetamide 、 3-氨基-5-环丙基-1H-吡唑 在 potassium hydrogencarbonate 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 13.0h， 生成 N-(4-chloro-6-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)-N-((3-isopropylisoxazol-5-yl)methyl)acetamide
  参考文献：
  名称：

  Process Development and Multikilogram Syntheses of XL228 Utilizing a Regioselective Isoxazole Formation and a Selective S_NAr Reaction to a Pyrimidine Core

  摘要：

  Route scouting, process development, and multikilogram syntheses of an IGF-1R/Src/Bcr-Abl inihibitor are reported. Key aspects of the developed route are a regioselective [3 + 2] isoxazole formation on a pyrimidine core and a selective SNAr addition of an aryl amine to a symmetrical dichloro substituted pyrimidine. The route contains six synthetic steps and was demonstrated twice on scale, delivering 4.6 and 11.2 kg (25% and 16% overall yield), for Phase I clinical studies.

  DOI：

  10.1021/op400137m
• 作为产物：
  描述：

  2-甲-1-硝丙烷 、 N-(4,6-dichloropyrimidin-2-yl)-N-(prop-2-ynyl)acetamide 在 对苯二异氰酸酯 、 三乙胺 作用下， 以 醋酸异丙酯 为溶剂， 反应 6.0h， 以92%的产率得到N-(4,6-dichloropyrimidin-2-yl)-N-((3-isopropylisoxazol-5-yl)methyl)acetamide
  参考文献：
  名称：

  Process Development and Multikilogram Syntheses of XL228 Utilizing a Regioselective Isoxazole Formation and a Selective S_NAr Reaction to a Pyrimidine Core

  摘要：

  Route scouting, process development, and multikilogram syntheses of an IGF-1R/Src/Bcr-Abl inihibitor are reported. Key aspects of the developed route are a regioselective [3 + 2] isoxazole formation on a pyrimidine core and a selective SNAr addition of an aryl amine to a symmetrical dichloro substituted pyrimidine. The route contains six synthetic steps and was demonstrated twice on scale, delivering 4.6 and 11.2 kg (25% and 16% overall yield), for Phase I clinical studies.

  DOI：

  10.1021/op400137m

文献信息

• Org. Process Res. Dev. 2013, 17, 1066-1073
  作者：

  DOI：——

  日期：——
• Process Development and Multikilogram Syntheses of XL228 Utilizing a Regioselective Isoxazole Formation and a Selective S_NAr Reaction to a Pyrimidine Core
  作者：Nathan R. Guz、Helena Leuser、Erick Goldman

  DOI：10.1021/op400137m

  日期：2013.8.16

  Route scouting, process development, and multikilogram syntheses of an IGF-1R/Src/Bcr-Abl inihibitor are reported. Key aspects of the developed route are a regioselective [3 + 2] isoxazole formation on a pyrimidine core and a selective SNAr addition of an aryl amine to a symmetrical dichloro substituted pyrimidine. The route contains six synthetic steps and was demonstrated twice on scale, delivering 4.6 and 11.2 kg (25% and 16% overall yield), for Phase I clinical studies.