2-(4-chlorophenyl)-3-oxoheptanenitrile | 96514-44-2

• 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: 2-(4-chlorophenyl)-3-oxoheptanenitrile
• 英文别名: 2-(4-Chlor-phenyl)-3-oxo-heptannitril
• CAS: 96514-44-2
• 化学式: C₁₃H₁₄ClNO
• 分子量: 235.713
• InChiKey: LYZBDSUATLPTIM-UHFFFAOYSA-N

物化性质

• 熔点：
  69-70 °C
• 沸点：
  323.2±27.0 °C(Predicted)
• 密度：
  1.133±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  40.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(4-chlorophenyl)-3-oxoheptanenitrile 在 碳酸氢钠 、 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 5.0h， 生成 5-(4-chlorophenyl)-6-butylpyrimidine-2,4-diamine
  参考文献：
  名称：

  Pyrimethamine Derivatives: Insight into Binding Mechanism and Improved Enhancement of Mutant β-N-acetylhexosaminidase Activity

  摘要：

  In order to identify structural features of pyrimethamine (5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine) that contribute to its inhibitory activity (IC50 value) and chaperoning efficacy toward beta-N-acetylhexosaminidase, derivatives of the compound were synthesized that differ at the positions bearing the amino, ethyl, and chloro groups. Whereas the amino groups proved to be critical to its inhibitory activity, a variety of substitutions at the chloro position only increased its IC50 by 2-3-fold. Replacing the ethyl group at the 6-position with butyl or methyl groups increased IC50 more than 10-fold. Surprisingly, despite its higher IC50, a derivative lacking the chlorine atom in the para-position was found to enhance enzyme activity in live patient cells a further 25% at concentrations >100 mu M, while showing less toxicity. These findings demonstrate the importance of the phenyl group in modulating the chaperoning efficacy and toxicity profile of the derivatives.

  DOI：

  10.1021/jm5017895
• 作为产物：
  描述：

  在 sodium perborate tetrahydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 以38.1 mg的产率得到2-(4-chlorophenyl)-3-oxoheptanenitrile
  参考文献：
  名称：

  配体控制的铜催化内部丙二烯的区域发散氰硼化

  摘要：

  已经开发出第一个铜催化的具有 B 2引脚2和 NCTS 衍生物的内部丙二烯区域发散氰基硼化反应。MeOH 被确定为 LCu-Bpin 物种再生的必要添加剂。计算研究表明，铜介导的烯丙基氰化作用是区域和立体决定步骤，而甲醇辅助的 B 2 pin 2金属转移是速率决定步骤。

  DOI：

  10.1002/anie.202210338

文献信息

• 2,4-Diaminopyrimidines as Antimalarials. III. 5-Aryl Derivatives
  作者：Peter B. Russell、George H. Hitchings

  DOI：10.1021/ja01152a060

  日期：1951.8
• Pyrimethamine Derivatives: Insight into Binding Mechanism and Improved Enhancement of Mutant β-<i>N</i>-acetylhexosaminidase Activity
  作者：Michael B. Tropak、Jianmin Zhang、Sayuri Yonekawa、Brigitte A. Rigat、Virender S. Aulakh、Matthew R. Smith、Hee-Jong Hwang、Marco A. Ciufolini、Don J. Mahuran

  DOI：10.1021/jm5017895

  日期：2015.6.11

  In order to identify structural features of pyrimethamine (5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine) that contribute to its inhibitory activity (IC50 value) and chaperoning efficacy toward beta-N-acetylhexosaminidase, derivatives of the compound were synthesized that differ at the positions bearing the amino, ethyl, and chloro groups. Whereas the amino groups proved to be critical to its inhibitory activity, a variety of substitutions at the chloro position only increased its IC50 by 2-3-fold. Replacing the ethyl group at the 6-position with butyl or methyl groups increased IC50 more than 10-fold. Surprisingly, despite its higher IC50, a derivative lacking the chlorine atom in the para-position was found to enhance enzyme activity in live patient cells a further 25% at concentrations >100 mu M, while showing less toxicity. These findings demonstrate the importance of the phenyl group in modulating the chaperoning efficacy and toxicity profile of the derivatives.
• Ligand‐Controlled Regiodivergent Cyanoboration of Internal Allenes by Copper Catalysis
  作者：Hui Hu、Guo‐Cui Ji、Linjuan Jiang、Siwei Bi、Yuan‐Ye Jiang、Yuanhong Liu

  DOI：10.1002/anie.202210338

  日期：2022.12.19

  The first copper-catalyzed regiodivergent cyanoboration of internal allenes with B2pin2 and NCTS derivatives has been developed. MeOH was identified as the necessary additive for the regeneration of LCu-Bpin species. Computational studies revealed that the copper-mediated allylic cyanation is the regio- and stereo-determining step, while the MeOH-assisted transmetalation with B2pin2 is the rate-determining

  已经开发出第一个铜催化的具有 B 2引脚2和 NCTS 衍生物的内部丙二烯区域发散氰基硼化反应。MeOH 被确定为 LCu-Bpin 物种再生的必要添加剂。计算研究表明，铜介导的烯丙基氰化作用是区域和立体决定步骤，而甲醇辅助的 B 2 pin 2金属转移是速率决定步骤。