(R)-6-(5-{[3-(benzyloxy)-2-(hydroxymethyl)propyl]-amino}-3-(4-fluorophenyl)-1H-pyrazol-4-yl)-2-(2-tolyl)-2,3-dihydropyridazin-3-one | 1404166-69-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (R)-6-(5-{[3-(benzyloxy)-2-(hydroxymethyl)propyl]-amino}-3-(4-fluorophenyl)-1H-pyrazol-4-yl)-2-(2-tolyl)-2,3-dihydropyridazin-3-one
• 英文别名: 6-[5-(4-fluorophenyl)-3-[[(2R)-2-(hydroxymethyl)-3-phenylmethoxypropyl]amino]-1H-pyrazol-4-yl]-2-(2-methylphenyl)pyridazin-3-one
• CAS: 1404166-69-3
• 化学式: C₃₁H₃₀FN₅O₃
• 分子量: 539.609
• InChiKey: CBPOPDURQITJQU-HSZRJFAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  103
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-6-(5-{[3-(benzyloxy)-2-(hydroxymethyl)propyl]-amino}-3-(4-fluorophenyl)-1H-pyrazol-4-yl)-2-(2-tolyl)-2,3-dihydropyridazin-3-one 在 吡啶 、 甲基磺酰氯 作用下， 以 乙腈 为溶剂， 反应 5.0h， 以85.1%的产率得到(R)-6-{6-[(benzyloxy)methyl]-2-(4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl}-2-(2-tolyl)-2,3-dihydropyridazin-3-one
  参考文献：
  名称：

  Development of a Practical and Scalable Synthesis of a Potent p38 Mitogen-Activated Protein Kinase Inhibitor

  摘要：

  Process research and development of a practical and scalable synthetic method toward a potent inhibitor of p38 mitogen-activated protein kinase 1 is described. The medicinal chemistry synthetic method had several issues in scale-up synthesis. In contrast, the synthetic method described here does not require purification by column chromatography for all steps, and the formation of impurities is suppressed well. Aminopyrazole ring formation was achieved by reaction between a new chiral amine building block 7 and bromoketone unit 4 as a key reaction. This highly efficient and scalable process was successfully demonstrated in the large-scale synthesis of 1.HBr.

  DOI：

  10.1021/op300237b
• 作为产物：
  描述：

  在 potassium dihydrogenphosphate 、 一水合肼 、 柠檬酸 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 40.0h， 生成 (R)-6-(5-{[3-(benzyloxy)-2-(hydroxymethyl)propyl]-amino}-3-(4-fluorophenyl)-1H-pyrazol-4-yl)-2-(2-tolyl)-2,3-dihydropyridazin-3-one
  参考文献：
  名称：

  Development of a Practical and Scalable Synthesis of a Potent p38 Mitogen-Activated Protein Kinase Inhibitor

  摘要：

  Process research and development of a practical and scalable synthetic method toward a potent inhibitor of p38 mitogen-activated protein kinase 1 is described. The medicinal chemistry synthetic method had several issues in scale-up synthesis. In contrast, the synthetic method described here does not require purification by column chromatography for all steps, and the formation of impurities is suppressed well. Aminopyrazole ring formation was achieved by reaction between a new chiral amine building block 7 and bromoketone unit 4 as a key reaction. This highly efficient and scalable process was successfully demonstrated in the large-scale synthesis of 1.HBr.

  DOI：

  10.1021/op300237b