2-chloro-N-(4-isopropyl-3-methylphenyl)nicotinamide | 1425782-74-6

• 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-chloro-N-(4-isopropyl-3-methylphenyl)nicotinamide
• 英文别名: 2-chloro-N-(3-methyl-4-propan-2-ylphenyl)pyridine-3-carboxamide
• CAS: 1425782-74-6
• 化学式: C₁₆H₁₇ClN₂O
• 分子量: 288.777
• InChiKey: QVPASKSKJJGIQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(4-isopropyl-3-methylphenyl)nicotinamide 、 7-氨基异喹啉 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 7.0h， 以79%的产率得到N-(4-isopropyl-3-methylphenyl)-2-(isoquinolin-7-ylamino)nicotinamide
  参考文献：
  名称：

  Development of a Scalable Synthesis of a VEGFR Inhibitor

  摘要：

  Process development and salt selection for a novel VEGFR inhibitor are described. The overall convergent synthesis involved coupling of three key fragments, 2-chloronicotinoyl chloride, 4-isopropyl-3-methylaniline and 7-aminoisoquinoline. A cost-effective and scalable synthesis of 7-aminoisoquinoline was also achieved. A transition-metal-free SNAr process enabled the final C-N coupling to afford the target molecule. A phosphate form of the drug substance with improved physical properties was selected for further development and the corresponding crystallization process was subsequently developed. Overall, a robust six-step route was developed and demonstrated on multikilogram scales affording the target compound in >30% yield and high purity (>99%).

  DOI：

  10.1055/s-0032-1317554
• 作为产物：
  描述：

  2-氯烟酰氯 、 4-异丙基-3-甲基苯胺盐酸盐 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以98%的产率得到2-chloro-N-(4-isopropyl-3-methylphenyl)nicotinamide
  参考文献：
  名称：

  Development of a Scalable Synthesis of a VEGFR Inhibitor

  摘要：

  Process development and salt selection for a novel VEGFR inhibitor are described. The overall convergent synthesis involved coupling of three key fragments, 2-chloronicotinoyl chloride, 4-isopropyl-3-methylaniline and 7-aminoisoquinoline. A cost-effective and scalable synthesis of 7-aminoisoquinoline was also achieved. A transition-metal-free SNAr process enabled the final C-N coupling to afford the target molecule. A phosphate form of the drug substance with improved physical properties was selected for further development and the corresponding crystallization process was subsequently developed. Overall, a robust six-step route was developed and demonstrated on multikilogram scales affording the target compound in >30% yield and high purity (>99%).

  DOI：

  10.1055/s-0032-1317554

文献信息

• Development of a Scalable Synthesis of a VEGFR Inhibitor
  作者：Ying Chen、Sheng Cui、Margaret Faul、Richard Crockett、Xin Wang、Robert Larsen

  DOI：10.1055/s-0032-1317554

  日期：——

  Process development and salt selection for a novel VEGFR inhibitor are described. The overall convergent synthesis involved coupling of three key fragments, 2-chloronicotinoyl chloride, 4-isopropyl-3-methylaniline and 7-aminoisoquinoline. A cost-effective and scalable synthesis of 7-aminoisoquinoline was also achieved. A transition-metal-free SNAr process enabled the final C-N coupling to afford the target molecule. A phosphate form of the drug substance with improved physical properties was selected for further development and the corresponding crystallization process was subsequently developed. Overall, a robust six-step route was developed and demonstrated on multikilogram scales affording the target compound in >30% yield and high purity (>99%).