(S)-N-benzyl-4-methyl-3-[1-(2,2,2-trifluoro-1-methylethoxy)phthalazin-6-yl]benzamide | 1114530-31-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (S)-N-benzyl-4-methyl-3-[1-(2,2,2-trifluoro-1-methylethoxy)phthalazin-6-yl]benzamide
• CAS: 1114530-31-2
• 化学式: C₂₆H₂₂F₃N₃O₂
• 分子量: 465.475
• InChiKey: VFNPGMOXUVCERU-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.86
• 重原子数：
  34.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  64.11
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  (S)-4-methyl-3-[1-(2,2,2-trifluoro-1-methylethoxy)phthalazin-6-yl]benzoic acid 、 苄胺 在 咪唑 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以87%的产率得到(S)-N-benzyl-4-methyl-3-[1-(2,2,2-trifluoro-1-methylethoxy)phthalazin-6-yl]benzamide
  参考文献：
  名称：

  Development of a Practical Synthesis of a p38 MAP Kinase Inhibitor

  摘要：

  A practical synthesis of the phthalazine-based p38 MAP kinase inhibitor [(S)-2] was needed for an ongoing program. Vibrational circular dichroism provided the assignment of the absolute stereochemistry of the target compound. The selected synthetic route for (S)-2 required identification of efficient reaction conditions for the construction of carbon-oxygen, carbon-carbon, and carbon-nitrogen bonds to connect the key building blocks. An efficient two-step method (chlorodehydroxylation, aromatic nucleophilic substitution) for the synthesis of arylether [(S)-10] was developed. PAT (in situ Raman spectroscopy) was utilized to monitor and control the formation of a lithium alkoxide in this reaction. The synthesis of (S)-2 was completed using high-yielding Suzuki- and amide-coupling reactions. The isolation conditions for these steps were optimized to obtain material of very high purity without the need for any complicated workup procedures.

  DOI：

  10.1021/op800250v