methyl (2S)-3-cyclopentyl-2-[5-(trifluoromethyl)imidazol-1-yl]propanoate | 1401513-86-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (2S)-3-cyclopentyl-2-[5-(trifluoromethyl)imidazol-1-yl]propanoate
• CAS: 1401513-86-7
• 化学式: C₁₃H₁₇F₃N₂O₂
• 分子量: 290.285
• InChiKey: CAONZJZWQLGUPG-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (R)-methyl 3-cyclopentyl-2-hydroxypropanoate 在 2,6-二甲基吡啶 、 potassium carbonate 作用下， 以 正己烷 、 乙酸乙酯 、 甲苯 为溶剂， 反应 5.33h， 生成 (S)-methyl 3-cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanoate 、 methyl (2S)-3-cyclopentyl-2-[5-(trifluoromethyl)imidazol-1-yl]propanoate
  参考文献：
  名称：

  Multikilogram Synthesis of a Hepatoselective Glucokinase Activator

  摘要：

  This work describes the process development and manufacture of early-stage clinical supplies of a hepatoselective glucokinase activator, a potential therapy for type 2 diabetes mellitus. Critical issues centered on challenges associated with the synthesis of intermediates and API bearing a particularly racemization-prone a-aryl carboxylate functionality. In particular, a T3P-mediated amidation process was optimized for the coupling of a racemization-prone acid substrate and a relatively non-nucleophilic amine. Furthermore, an unusually hydrolytically-labile amide in the API also complicated the synthesis and isolation of drug substance. The evolution of the process over multiple campaigns is presented, resulting in the preparation of over 110 kg of glucokinase activator.

  DOI：

  10.1021/op300194c

文献信息

• Multikilogram Synthesis of a Hepatoselective Glucokinase Activator
  作者：Joshua R. Dunetz、Martin A. Berliner、Yanqiao Xiang、Timothy L. Houck、Fabrice H. Salingue、Wang Chao、Chen Yuandong、Wang Shenghua、Yun Huang、Douglas Farrand、Steven J. Boucher、David B. Damon、Teresa W. Makowski、Mark T. Barrila、Raymond Chen、Isamir Martínez

  DOI：10.1021/op300194c

  日期：2012.10.19

  This work describes the process development and manufacture of early-stage clinical supplies of a hepatoselective glucokinase activator, a potential therapy for type 2 diabetes mellitus. Critical issues centered on challenges associated with the synthesis of intermediates and API bearing a particularly racemization-prone a-aryl carboxylate functionality. In particular, a T3P-mediated amidation process was optimized for the coupling of a racemization-prone acid substrate and a relatively non-nucleophilic amine. Furthermore, an unusually hydrolytically-labile amide in the API also complicated the synthesis and isolation of drug substance. The evolution of the process over multiple campaigns is presented, resulting in the preparation of over 110 kg of glucokinase activator.