sodium (S)-4-methyl-3-[1-(2,2,2-trifluoro-1-methylethoxy)phthalazin-6-yl]benzoate | 1114530-30-1

• 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: sodium (S)-4-methyl-3-[1-(2,2,2-trifluoro-1-methylethoxy)phthalazin-6-yl]benzoate
• 英文别名: sodium;4-methyl-3-[1-[(2S)-1,1,1-trifluoropropan-2-yl]oxyphthalazin-6-yl]benzoate
• CAS: 1114530-30-1
• 化学式: C₁₉H₁₄F₃N₂O₃*Na
• 分子量: 398.317
• InChiKey: ZAKYCKDEMRLTKK-MERQFXBCSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  75.1
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  sodium (S)-4-methyl-3-[1-(2,2,2-trifluoro-1-methylethoxy)phthalazin-6-yl]benzoate 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以100%的产率得到(S)-4-methyl-3-[1-(2,2,2-trifluoro-1-methylethoxy)phthalazin-6-yl]benzoic acid
  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
• 作为产物：
  描述：

  2-甲基-5-羟基羰基-3-硼酸 、 (S)-6-chloro-1-(2,2,2-trifluoro-1-methylethoxy)phthalazine 在 2-双环己基膦-2',6'-二甲氧基联苯 、 tris(dibenzylideneacetone)dipalladium (0) 、 sodium carbonate 作用下， 以 乙醇 、 水 为溶剂， 80.0 ℃ 、106.87 kPa 条件下， 反应 17.0h， 以90%的产率得到sodium (S)-4-methyl-3-[1-(2,2,2-trifluoro-1-methylethoxy)phthalazin-6-yl]benzoate
  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