methyl 5-fluoro-2-(isobutylamino)pyrimidine-4-carboxylate | 1381840-03-4

• 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: methyl 5-fluoro-2-(isobutylamino)pyrimidine-4-carboxylate
• CAS: 1381840-03-4
• 化学式: C₁₀H₁₄FN₃O₂
• 分子量: 227.238
• InChiKey: RRXQGAJIPJQRRH-UHFFFAOYSA-N

物化性质

• 沸点：
  344.1±52.0 °C(Predicted)
• 密度：
  1.213±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.47
• 重原子数：
  16.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  64.11
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  methyl 5-fluoro-2-(isobutylamino)pyrimidine-4-carboxylate 在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 5.0h， 以86%的产率得到5-fluoro-2-isobutylaminopyrimidine-4-carboxylic acid
  参考文献：
  名称：

  Facile and regioselective synthesis of novel 2,4-disubstituted-5-fluoropyrimidines as potential kinase inhibitors

  摘要：

  2,4-Disubstituted-5-fluoropyrimidine is a biologically active molecular core seen in various anticancer agents such as 5-fluorouracil (5-FU). As part of a programme aimed at discovering kinase inhibitors, routes to two series of novel compounds (5-fluoropyrimidine-2-carboxamides and 5-fluoropyrimidine-4-carboxamides) were successfully executed. For the first series, regioselective substitution at the 4-position of the pyrimidine with an amine ((HNRR2)-R-1) was achieved, followed by preparation of the amide at the 2-position. The route to the second series involved introduction of the methoxy protecting group at the 4-position, which allowed subsequent amine substitution to occur at the 2-position. The 4-amide substituent was finally introduced by direct conversion of the 4-methoxy into a 4-chloro group followed by transformation into an amide by palladium catalysis. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.01.088
• 作为产物：
  描述：

  (5-fluoro-4-methoxypyrimidin-2-yl)isobutylamine 在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 三乙胺 、 三氯氧磷 作用下， 以 水 为溶剂， 50.0~100.0 ℃ 、344.75 kPa 条件下， 反应 48.0h， 生成 methyl 5-fluoro-2-(isobutylamino)pyrimidine-4-carboxylate
  参考文献：
  名称：

  Facile and regioselective synthesis of novel 2,4-disubstituted-5-fluoropyrimidines as potential kinase inhibitors

  摘要：

  2,4-Disubstituted-5-fluoropyrimidine is a biologically active molecular core seen in various anticancer agents such as 5-fluorouracil (5-FU). As part of a programme aimed at discovering kinase inhibitors, routes to two series of novel compounds (5-fluoropyrimidine-2-carboxamides and 5-fluoropyrimidine-4-carboxamides) were successfully executed. For the first series, regioselective substitution at the 4-position of the pyrimidine with an amine ((HNRR2)-R-1) was achieved, followed by preparation of the amide at the 2-position. The route to the second series involved introduction of the methoxy protecting group at the 4-position, which allowed subsequent amine substitution to occur at the 2-position. The 4-amide substituent was finally introduced by direct conversion of the 4-methoxy into a 4-chloro group followed by transformation into an amide by palladium catalysis. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.01.088