6-[2-tert-butyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-1-(propane-2-sulfonyl)-1H-benzoimidazol-2-ylamine monomesylate | 849064-43-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-[2-tert-butyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-1-(propane-2-sulfonyl)-1H-benzoimidazol-2-ylamine monomesylate
• 英文别名: 6-[2-tert-butyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-1-propan-2-ylsulfonylbenzimidazol-2-amine;methanesulfonic acid
• CAS: 849064-43-3
• 化学式: CH₄O₃S*C₂₃H₂₅F₂N₅O₂S
• 分子量: 569.654
• InChiKey: MUOZIXHHNYUODU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.34
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  178
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  1-乙炔基-2,4-二氟苯 在 potassium permanganate 、 二乙酰二(三苯基膦)钯 、 ammonium acetate 、 碳酸氢钠 、 magnesium sulfate 、 三乙胺 作用下， 以 甲醇 、 水 、 二甲基亚砜 、 丙酮 、 正丁醇 为溶剂， 反应 45.17h， 生成 6-[2-tert-butyl-5-(2,4-difluorophenyl)-1H-imidazol-4-yl]-1-(propane-2-sulfonyl)-1H-benzoimidazol-2-ylamine monomesylate
  参考文献：
  名称：

  Synthesis of Imidazole Based p38 MAP (Mitogen-Activated Protein) Kinase Inhibitors under Buffered Conditions

  摘要：

  This article describes chemistry that was developed to give access to multigram quantities of imidazole 479754 and several related analogues for Eli Lilly's p38 MAPK program targeting therapies to address inflammation. The molecules of interest have an isopropyl sulfonyl group present on the 2-aminobenzimidazole heterocycyle that was found to be labile when heated in polar solvents and/or exposed to high or low pH. Due to this instability issue, the syntheses of the target molecules required optimizing Sonogashira reaction conditions, employing a buffered oxidative method to produce alpha-diones, developing buffered reaction conditions to generate imidazoles, and developing final recrystallization conditions.

  DOI：

  10.1021/op060042t

文献信息

• Synthesis of Imidazole Based p38 MAP (Mitogen-Activated Protein) Kinase Inhibitors under Buffered Conditions
  作者：Nicholas A. Magnus、William D. Diseroad、C. Richard Nevill、James P. Wepsiec

  DOI：10.1021/op060042t

  日期：2006.5.1

  This article describes chemistry that was developed to give access to multigram quantities of imidazole 479754 and several related analogues for Eli Lilly's p38 MAPK program targeting therapies to address inflammation. The molecules of interest have an isopropyl sulfonyl group present on the 2-aminobenzimidazole heterocycyle that was found to be labile when heated in polar solvents and/or exposed to high or low pH. Due to this instability issue, the syntheses of the target molecules required optimizing Sonogashira reaction conditions, employing a buffered oxidative method to produce alpha-diones, developing buffered reaction conditions to generate imidazoles, and developing final recrystallization conditions.