5-((5-bromopyridin-2-yl)oxy)-2-fluoroaniline | 1514914-92-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-((5-bromopyridin-2-yl)oxy)-2-fluoroaniline
• CAS: 1514914-92-1
• 化学式: C₁₁H₈BrFN₂O
• 分子量: 283.1
• InChiKey: HMNPOCPBQQMZSY-UHFFFAOYSA-N

物化性质

• 沸点：
  357.7±42.0 °C(predicted)
• 密度：
  1.609±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.36
• 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：
  0.0
• 拓扑面积：
  48.14
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  2-chloro-4-fluorophenyl methyl carbonate 在 甲醇 、 potassium phosphate 、 硫酸 、 palladium 10% on activated carbon 、 氢气 、 硝酸 、 sodium acetate 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 二甲基亚砜 为溶剂， 反应 15.67h， 生成 5-((5-bromopyridin-2-yl)oxy)-2-fluoroaniline
  参考文献：
  名称：

  Development of a Scalable Synthesis of a Vascular Endothelial Growth Factor Receptor-2 Kinase Inhibitor: Efficient Construction of a 6-Etherified [1,2,4]Triazolo[1,5-a]pyridine-2-amine Core

  摘要：

  A practical and scalable synthesis of the vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibitor 1 has been developed. The key features of the process development include facile preparation of the key raw material 3-amino-4-fluorophenol, chemoselective nucleophilic aromatic substitution of 5-chloro-2-nitropyridine with phenol, a safe one-pot synthesis of a substituted urea using an isothiocyanate generated in situ from inexpensive materials, and improvement of the yield of acylation in the end game. The optimized six-step synthesis afforded 1:H2O in 54% overall yield, twice as much as the yield of the original synthesis, without chromatographic purification. In addition, a robust recrystallization procedure to afford the desired crystal form of 1 was also developed.

  DOI：

  10.1021/op4002824