(4-(4-fluorophenyl)-6-isopropyl-2-(methyl(1-methyl-1H-1,2,4-triazol-5-yl)amino)pyrimidine-5-yl)methanol | 1218994-93-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (4-(4-fluorophenyl)-6-isopropyl-2-(methyl(1-methyl-1H-1,2,4-triazol-5-yl)amino)pyrimidine-5-yl)methanol
• 英文别名: [4-(4-Fluorophenyl)-2-[methyl-(2-methyl-1,2,4-triazol-3-yl)amino]-6-propan-2-ylpyrimidin-5-yl]methanol
• CAS: 1218994-93-4
• 化学式: C₁₈H₂₁FN₆O
• 分子量: 356.403
• InChiKey: YNKOEMNDHFPTND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  80
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (4-(4-fluorophenyl)-6-isopropyl-2-(methyl(1-methyl-1H-1,2,4-triazol-5-yl)amino)pyrimidine-5-yl)methanol 在 sodium hypochlorite 、 1-羟基-2,2,6,6-四甲基哌啶 、 potassium bromide 作用下， 以 水 、 乙酸乙酯 为溶剂， 以93.5%的产率得到4-(4-fluorophenyl)-6-isopropyl-2-(methyl(1-methyl-1H-1,2,4-triazol-5-yl)amino)pyrimidine-5-carbaldehyde
  参考文献：
  名称：

  Development of a Scaleable Process for the Synthesis of a Next-Generation Statin

  摘要：

  This manuscript details life process research and development of a convergent and safe approach to 1 on a multikilo scale. Specific highlights of the process development efforts will be described, including the development of a dehydrogenation method for dihydropyrimidines and a thermochemically safe synthesis of a 1,2,4-aminotriazole fragment. A key feature of the synthesis is the use and optimization of a modified Julia-Kocienski olefination reaction. Specifically, we report an unprecedented dependence of the product olefin geometry on reaction temperature, where an E:Z ratio as high as 200:1 can be obtained. Initial insights into the mechanistic rationale for this observation are also provided. Finally, a purity upgrade sequence via an intermediate crystalline form is highlighted is a method of controlling the final API quality.

  DOI：

  10.1021/op100010n
• 作为产物：
  描述：

  methyl 4-(4-fluorophenyl)-2-[methyl-(2-methyl-1,2,4-triazol-3-yl)amino]-6-propan-2-ylpyrimidine-5-carboxylate 在 二异丁基氢化铝 作用下， 以 甲苯 为溶剂， 以14.71 kg的产率得到(4-(4-fluorophenyl)-6-isopropyl-2-(methyl(1-methyl-1H-1,2,4-triazol-5-yl)amino)pyrimidine-5-yl)methanol
  参考文献：
  名称：

  Development of a Scaleable Process for the Synthesis of a Next-Generation Statin

  摘要：

  This manuscript details life process research and development of a convergent and safe approach to 1 on a multikilo scale. Specific highlights of the process development efforts will be described, including the development of a dehydrogenation method for dihydropyrimidines and a thermochemically safe synthesis of a 1,2,4-aminotriazole fragment. A key feature of the synthesis is the use and optimization of a modified Julia-Kocienski olefination reaction. Specifically, we report an unprecedented dependence of the product olefin geometry on reaction temperature, where an E:Z ratio as high as 200:1 can be obtained. Initial insights into the mechanistic rationale for this observation are also provided. Finally, a purity upgrade sequence via an intermediate crystalline form is highlighted is a method of controlling the final API quality.

  DOI：

  10.1021/op100010n