methyl (4-(4-fluorophenyl)-6-isopropyl-2-(1-methyl-1H-1,2,4-triazol-5-yl)amino)pyrimidine-5-carboxylate | 1218994-92-3

• 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: methyl (4-(4-fluorophenyl)-6-isopropyl-2-(1-methyl-1H-1,2,4-triazol-5-yl)amino)pyrimidine-5-carboxylate
• 英文别名: Methyl 4-(4-fluorophenyl)-2-[(2-methyl-1,2,4-triazol-3-yl)amino]-6-propan-2-ylpyrimidine-5-carboxylate
• CAS: 1218994-92-3
• 化学式: C₁₈H₁₉FN₆O₂
• 分子量: 370.386
• InChiKey: RFEXQGYNYKNNGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  94.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  甲基2-氯-4-(4-氟苯基)-6-异丙基嘧啶-5-羧酸 、 1-甲基-1H-1,2,4-噻唑-5-胺 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以86%的产率得到methyl (4-(4-fluorophenyl)-6-isopropyl-2-(1-methyl-1H-1,2,4-triazol-5-yl)amino)pyrimidine-5-carboxylate
  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