2-chloro-N-cyclopentyl-5-(iodoethynyl)pyrimidin-4-amine | 1383481-57-9

• 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: 2-chloro-N-cyclopentyl-5-(iodoethynyl)pyrimidin-4-amine
• CAS: 1383481-57-9
• 化学式: C₁₁H₁₁ClIN₃
• 分子量: 347.586
• InChiKey: QOWJJNLWNBCLES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.23
• 重原子数：
  16.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  37.81
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-chloro-N-cyclopentyl-5-(iodoethynyl)pyrimidin-4-amine 在 四(三苯基膦)钯 、 四丁基氟化铵 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-chloro-7-cyclopentyl-6-(1-isopentyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Structure-based design of 2,6,7-trisubstituted-7H-pyrrolo[2,3-d]pyrimidines as Aurora kinases inhibitors

  摘要：

  This Letter reports the optimization of a pyrrolopyrimidine series as dual inhibitors of Aurora A/B kinases. This series derived from a pyrazolopyrimidine series previously reported as inhibitors of aurora kinases and CDKs. In an effort to improve the selectivity of this chemotype, we switched to the pyrrolopyrimidine core which allowed functionalization on C-2. In addition, the modeling rationale was based on superimposing the structures of Aurora-A kinase and CDK2 which revealed enough differences leading to a path for selectivity improvement. The synthesis of the new series of pyrrolopyrimidine analogs relied on the development of a different route for the two key intermediates 7 and 19 which led to analogs with both tunable activity against CDK1 and maintained cell potency. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.085
• 作为产物：
  描述：

  2-chloro-N-cyclopentyl-5-((trimethylsilyl)ethynyl)pyrimidin -4-amine 在 N-碘代丁二酰亚胺 、 silver nitrate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以68%的产率得到2-chloro-N-cyclopentyl-5-(iodoethynyl)pyrimidin-4-amine
  参考文献：
  名称：

  Structure-based design of 2,6,7-trisubstituted-7H-pyrrolo[2,3-d]pyrimidines as Aurora kinases inhibitors

  摘要：

  This Letter reports the optimization of a pyrrolopyrimidine series as dual inhibitors of Aurora A/B kinases. This series derived from a pyrazolopyrimidine series previously reported as inhibitors of aurora kinases and CDKs. In an effort to improve the selectivity of this chemotype, we switched to the pyrrolopyrimidine core which allowed functionalization on C-2. In addition, the modeling rationale was based on superimposing the structures of Aurora-A kinase and CDK2 which revealed enough differences leading to a path for selectivity improvement. The synthesis of the new series of pyrrolopyrimidine analogs relied on the development of a different route for the two key intermediates 7 and 19 which led to analogs with both tunable activity against CDK1 and maintained cell potency. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.085