(5-(4-propoxy-2-(trifluoromethyl)phenyl)pyrimidin-2-yl)methyl methanesulfonate | 1494718-09-0

• 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: (5-(4-propoxy-2-(trifluoromethyl)phenyl)pyrimidin-2-yl)methyl methanesulfonate
• CAS: 1494718-09-0
• 化学式: C₁₆H₁₇F₃N₂O₄S
• 分子量: 390.383
• InChiKey: UCQHVZUBKPXECU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.43
• 重原子数：
  26.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  78.38
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2-(2,3-difluorophenyl)-5H-imidazo[4,5-d]pyridazine 、 (5-(4-propoxy-2-(trifluoromethyl)phenyl)pyrimidin-2-yl)methyl methanesulfonate 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以38 mg的产率得到2-(2,3-difluorophenyl)-5-((5-(4-propoxy-2-(trifluoromethyl)phenyl)pyrimidin-2-yl)methyl)-5H-imidazo[4,5-d]pyridazine
  参考文献：
  名称：

  Imidazopyridazine Hepatitis C Virus Polymerase Inhibitors. Structure–Activity Relationship Studies and the Discovery of a Novel, Traceless Prodrug Mechanism

  摘要：

  By reducing the basicity of the core heterocycle in a series of HCV NS5B inhibitors, the hERG liability was reduced. The SAR was then systematically explored in order to increase solubility and enable dose escalation while retaining potency. During this exploration, a facile decarboxylation was noted and was exploited as a novel prodnig mechanism. The synthesis and characterization of these prodrugs and their utilization in chronic toxicity studies are presented.

  DOI：

  10.1021/jm401337x
• 作为产物：
  描述：

  4-丙氧基-2-(三氟甲基)苯硼酸 在 四(三苯基膦)钯 、 甲酸 、 sodium carbonate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 37.0h， 生成 (5-(4-propoxy-2-(trifluoromethyl)phenyl)pyrimidin-2-yl)methyl methanesulfonate
  参考文献：
  名称：

  Imidazopyridazine Hepatitis C Virus Polymerase Inhibitors. Structure–Activity Relationship Studies and the Discovery of a Novel, Traceless Prodrug Mechanism

  摘要：

  By reducing the basicity of the core heterocycle in a series of HCV NS5B inhibitors, the hERG liability was reduced. The SAR was then systematically explored in order to increase solubility and enable dose escalation while retaining potency. During this exploration, a facile decarboxylation was noted and was exploited as a novel prodnig mechanism. The synthesis and characterization of these prodrugs and their utilization in chronic toxicity studies are presented.

  DOI：

  10.1021/jm401337x