(2S)-2-(3-bromo-4-((7-methoxy-2-phenylquinolin-4-yl)oxy)phenyl)-2-((tert-butoxycarbonyl)amino)acetic acid | 1241589-35-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (2S)-2-(3-bromo-4-((7-methoxy-2-phenylquinolin-4-yl)oxy)phenyl)-2-((tert-butoxycarbonyl)amino)acetic acid
• CAS: 1241589-35-4
• 化学式: C₂₉H₂₇BrN₂O₆
• 分子量: 579.447
• InChiKey: ZLRRYNOVBVHPFX-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.12
• 重原子数：
  38.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  106.98
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2,4,6-trivinylcycloboroxane pyridine complex 、 (2S)-2-(3-bromo-4-((7-methoxy-2-phenylquinolin-4-yl)oxy)phenyl)-2-((tert-butoxycarbonyl)amino)acetic acid 在 水 、 palladium diacetate 、 potassium carbonate 、 tri tert-butylphosphoniumtetrafluoroborate 、 盐酸 作用下， 以 乙二醇二甲醚 为溶剂， 反应 0.25h， 以34%的产率得到2-((tert-butoxycarbonyl)amino)-2-(4-((7-methoxy-2-phenylquinolin-4-yl)oxy)-3-vinylphenyl)acetic acid
  参考文献：
  名称：

  Improved P2 phenylglycine-based hepatitis C virus NS3 protease inhibitors with alkenylic prime-side substituents

  摘要：

  Phenylglycine has proved to be a useful P2 residue in HCV NS3 protease inhibitors. A novel pi-pi-interaction between the phenylglycine and the catalytic H57 residue of the protease is postulated. We hypothesized that the introduction of a vinyl on the phenylglycine might strengthen this pi-pi-interaction. Thus, herein is presented the synthesis and inhibitory potency of a series of acyclic vinylated phenylglycine-based HCV NS3 protease inhibitors. Surprisingly, inhibitors based on both D-and L-phenylglycine were found to be effective inhibitors, with a slight preference for the D-epimers. Furthermore, prime-side alkenylic extension of the C-terminal acylsulfonamide group gave significantly improved inhibitors with potencies in the nanomolar range (similar to 35 nM), potencies which were retained on mutant variants of the protease. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.05.027
• 作为产物：
  描述：

  在 tris-(dibenzylideneacetone)dipalladium(0) 、 2-二叔丁基膦-2′,4′,6′-三异丙基-3,6-二甲氧基-1,1′-联苯 、 potassium tert-butylate 、 cesium fluoride 作用下， 以 1,4-二氧六环 、 二甲基亚砜 、 甲苯 为溶剂， 反应 6.67h， 生成 (2S)-2-(3-bromo-4-((7-methoxy-2-phenylquinolin-4-yl)oxy)phenyl)-2-((tert-butoxycarbonyl)amino)acetic acid
  参考文献：
  名称：

  One-Pot, Two-Step, Microwave-Assisted Palladium-Catalyzed Conversion of Aryl Alcohols to Aryl Fluorides via Aryl Nonaflates

  摘要：

  A convenient procedure for converting aryl alcohols to aryl fluorides via aryl nonafluorobutylsulfonates (ArONf) is presented. Moderate to good one-pot, two-step yields were achieved by this nonaflation and microwave-assisted, palladium-catalyzed fluorination sequence. The reductive elimination step was investigated by DFT calculations to compare fluorination with chlorination, proving a larger thermodynamic driving force for the aryl fluoride product. Finally, a key aryl fluoride intermediate for the synthesis of a potent HCV NS3 protease inhibitor was smoothly prepared with the novel protocol.

  DOI：

  10.1021/jo400255m