tert-butyl 2-(4-(trifluoromethyl)-1H-imidazol-1-yl)acetate | 1191255-78-3

• 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: tert-butyl 2-(4-(trifluoromethyl)-1H-imidazol-1-yl)acetate
• CAS: 1191255-78-3
• 化学式: C₁₀H₁₃F₃N₂O₂
• 分子量: 250.221
• InChiKey: XDHIFNADCGVRKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.24
• 重原子数：
  17.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  44.12
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-(4-(trifluoromethyl)-1H-imidazol-1-yl)acetate 在 bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate 、 (S,R)-PPF-P(t-Bu)2 、 氢气 、 甲基磺酰氯 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 生成
  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
• 作为产物：
  描述：

  溴乙酸叔丁酯 、 4-(三氟甲基)-1H-咪唑 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以80%的产率得到tert-butyl 2-(4-(trifluoromethyl)-1H-imidazol-1-yl)acetate
  参考文献：
  名称：

  Optimization of a series of quinazolinone-derived antagonists of CXCR3

  摘要：

  The evaluation of the CXCR3 antagonist AMG 487 in clinic trials was complicated due to the formation of an active metabolite. In this Letter, we will discuss the further optimization of the quinazolinone series that led to the discovery of compounds devoid of the formation of the active metabolite that was seen with AMG 487. In addition, these compounds also feature increased potency and good pharmacokinetic properties. We will also discuss the efficacy of the lead compound 34 in a mouse model of cellular recruitment induced by bleomycin. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.032