依曲韦林杂质2 | 1225383-64-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 依曲韦林杂质2
• 英文名称: 4-[2-Chloro-6-(4-cyanoanilino)pyrimidin-4-yl]oxy-3,5-dimethylbenzonitrile
• CAS: 1225383-64-1
• 化学式: C₂₀H₁₄ClN₅O
• 分子量: 375.817
• InChiKey: CVCIISGTGYWJHF-UHFFFAOYSA-N

物化性质

• 沸点：
  618.4±55.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.03
• 重原子数：
  27.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  94.62
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  3,5-二甲基-4-羟基苯甲腈 在 potassium tert-butylate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 为溶剂， 反应 4.0h， 生成 依曲韦林中间体 、 依曲韦林杂质2
  参考文献：
  名称：

  An Improved Synthesis of Etravirine

  摘要：

  Etravirine (1) is a novel diarylpyrimidine non-nucleoside reverse transcriptase inhibitor and has recently been approved by the U.S. Federal Drug Administsration for the treatment of AIDS. Its reported synthesis is fraught with many difficulties, the foremost being the poor yield and long reaction time required at the aminolysis stage. We attributed this problem to the presence of a bromide group adjacent to the reaction site of the advance intermediate (6). In order to circumvent this issue, we proposed to defer the installation of the bromide group at a later stage, preferably after aminolysis. Indeed, this protocol has worked well. However, in the process of installation of diarylether and diary-amine functionalities at appropriate positions, we had to reverse the sequence of displacement reactions of the dichloride intermediate (9) with 3,5-dimethyl-4-hydroxybenzonitrile (5) and 4-aminobenzonitrile (3). The classical bromination led to the completion of etravirine synthesis.

  DOI：

  10.1021/op9003289