(R)-2-chloro-5-fluoro-4-((1-(3-fluorophenyl)propan-2-yl)oxy)pyrimidine | 1149745-46-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-2-chloro-5-fluoro-4-((1-(3-fluorophenyl)propan-2-yl)oxy)pyrimidine
• CAS: 1149745-46-9
• 化学式: C₁₃H₁₁ClF₂N₂O
• 分子量: 284.693
• InChiKey: YAIWDRLPKSTVGG-MRVPVSSYSA-N

物化性质

• 沸点：
  422.5±40.0 °C(predicted)
• 密度：
  1.328±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.42
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  35.01
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (R)-2-chloro-5-fluoro-4-((1-(3-fluorophenyl)propan-2-yl)oxy)pyrimidine 、 (R)-4-Boc-2-甲基哌嗪 在 三乙胺 作用下， 以 甲苯 为溶剂， 以60%的产率得到tert-butyl (R)-4-(5-fluoro-4-(((R)-1-(3-fluorophenyl)propan-2-yl)oxy)pyrimidin-2-yl)-3-methylpiperazine-1-carboxylate
  参考文献：
  名称：

  Biochemical basis for differences in metabolism-dependent genotoxicity by two diazinylpiperazine-based 5-HT2C receptor agonists

  摘要：

  The biochemical basis for S9-dependent mutagenic response of the 5-HT2C receptor agonist and diazinylpiperazine derivative 1 in the Salmonella Ames assay involves P450-mediated bioactivation to DNA-reactive quinone-methide, aldehyde and nitrone intermediates. Mechanistic information pertaining to the metabolism of 1 was used in the design of diazinylpiperazine 5 to eliminate the safety liability. While 5 was negative in the Ames assay, the compound retained the ability of 1 to form certain electrophilic intermediates. Plausible hypotheses that can collectively account for the differences in mutagenic response of the two piperazine analogs are discussed. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.02.032
• 作为产物：
  描述：

  (2R)-1-(3-fluorophenyl)propan-2-ol 、 2,4-二氯-5-氟嘧啶 在 sodium t-butanolate 作用下， 以 甲苯 为溶剂， 以82%的产率得到(R)-2-chloro-5-fluoro-4-((1-(3-fluorophenyl)propan-2-yl)oxy)pyrimidine
  参考文献：
  名称：

  Biochemical basis for differences in metabolism-dependent genotoxicity by two diazinylpiperazine-based 5-HT2C receptor agonists

  摘要：

  The biochemical basis for S9-dependent mutagenic response of the 5-HT2C receptor agonist and diazinylpiperazine derivative 1 in the Salmonella Ames assay involves P450-mediated bioactivation to DNA-reactive quinone-methide, aldehyde and nitrone intermediates. Mechanistic information pertaining to the metabolism of 1 was used in the design of diazinylpiperazine 5 to eliminate the safety liability. While 5 was negative in the Ames assay, the compound retained the ability of 1 to form certain electrophilic intermediates. Plausible hypotheses that can collectively account for the differences in mutagenic response of the two piperazine analogs are discussed. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.02.032