N-(4-isopropyl-3-methylphenyl)-2-(isoquinolin-7-ylamino)nicotinamide | 1425782-76-8

• 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: N-(4-isopropyl-3-methylphenyl)-2-(isoquinolin-7-ylamino)nicotinamide
• 英文别名: 2-(isoquinolin-7-ylamino)-N-(3-methyl-4-propan-2-ylphenyl)pyridine-3-carboxamide;phosphoric acid
• CAS: 1425782-76-8
• 化学式: C₂₅H₂₄N₄O*H₃O₄P
• 分子量: 494.487
• InChiKey: AMWRTMUCKIZLEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.13
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  145
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  7-硝基-3,4-二氢异喹啉 在 manganese(IV) oxide 、 磷酸 、 palladium 10% on activated carbon 、 氢气 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 35.0h， 生成 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

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%).