4-(4-fluorophenyl)-6-isopropyl-2-(methyl(1-methyl-1H-1,2,4-triazol-5-yl)amino)pyrimidine-5-carbaldehyde | 1218994-94-5

• 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-carbaldehyde
• 英文别名: 4-(4-Fluorophenyl)-2-[methyl-(2-methyl-1,2,4-triazol-3-yl)amino]-6-propan-2-ylpyrimidine-5-carbaldehyde
• CAS: 1218994-94-5
• 化学式: C₁₈H₁₉FN₆O
• 分子量: 354.387
• InChiKey: MSGAOCIMTBGYJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  76.8
• 氢给体数：
  0
• 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-carbaldehyde 在 盐酸 、 sodium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 正庚烷 、 水 、 乙腈 为溶剂， 反应 3.17h， 生成 ammonium (3R,5S,E)-7-(4-(4-fluorophenyl)-6-isopropyl-2-(methyl(1-methyl-1H-1,2,4-triazol-5-yl)amino)pyrimidin-5-yl)-3,5-dihydroxyhept-6-enoate
  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)-6-isopropyl-2-(1-methyl-1H-1,2,4-triazol-5-yl)amino)pyrimidine-5-carboxylate 在 三乙烯二胺 、 sodium hypochlorite 、 1-羟基-2,2,6,6-四甲基哌啶 、 二异丁基氢化铝 、 potassium bromide 作用下， 以 水 、 乙酸乙酯 、 甲苯 为溶剂， 生成 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