苯磺酸,N,2-二甲基-6-[2-(1-甲基咪唑-2-基)噻吩并[3,2-b]吡啶-7-基]氧代-1-苯并噻吩-3-甲酰胺 | 881688-70-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 苯磺酸,N,2-二甲基-6-[2-(1-甲基咪唑-2-基)噻吩并[3,2-b]吡啶-7-基]氧代-1-苯并噻吩-3-甲酰胺
• 英文名称: N,2-dimethyl-6-(2-(1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)benzo[b]thiophene-3-carboxamide benzenesulfonic acid salt
• 英文别名: AG-28262 besylate；benzenesulfonic acid;N,2-dimethyl-6-[2-(1-methylimidazol-2-yl)thieno[3,2-b]pyridin-7-yl]oxy-1-benzothiophene-3-carboxamide
• CAS: 881688-70-6
• 化学式: C₆H₆O₃S*C₂₂H₁₈N₄O₂S₂
• 分子量: 592.72
• InChiKey: BZZKDMVEPMDMQA-UHFFFAOYSA-N

物化性质

• 熔点：
  237.3-239.2 °C

计算性质

• 辛醇/水分配系数(LogP)：
  6.31
• 重原子数：
  40
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  188
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  Imidazol-1-yl-(6-methoxy-2-methyl-1-benzothiophen-3-yl)methanone 在 caesium carbonate 、 DL-蛋氨酸 作用下， 以 四氢呋喃 、 甲烷磺酸 、 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 49.5h， 生成 苯磺酸,N,2-二甲基-6-[2-(1-甲基咪唑-2-基)噻吩并[3,2-b]吡啶-7-基]氧代-1-苯并噻吩-3-甲酰胺
  参考文献：
  名称：

  Development of a Scalable Synthesis to VEGFR Inhibitor AG-28262

  摘要：

  The synthesis of N,2-dimethyl-6-(2-(1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)benzo[b]thiophene-3-carboxamide (1, AG-28262) on kilogram scale is described. Initial syntheses of key components 2 and 3 worked well on laboratory scale but had significant drawbacks for larger-scale manufacture. Therefore, new routes to these two key fragments were developed and demonstrated to synthesize kilogram quantities. Key steps involve a two-step thiophenol alkylation/cyclization protocol to synthesize 2 in a convergent manner. A difficult Pd-mediated coupling to produce 3 was replaced with a more scalable stepwise imidazole synthesis. Key rationale for the new routes are discussed.

  DOI：

  10.1021/op0502396

文献信息

• Development of a Scalable Synthesis to VEGFR Inhibitor AG-28262
  作者：Robert W. Scott、Sean N. Neville、Armando Urbina、David Camp、Nebojsa Stankovic

  DOI：10.1021/op0502396

  日期：2006.3.1

  The synthesis of N,2-dimethyl-6-(2-(1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)benzo[b]thiophene-3-carboxamide (1, AG-28262) on kilogram scale is described. Initial syntheses of key components 2 and 3 worked well on laboratory scale but had significant drawbacks for larger-scale manufacture. Therefore, new routes to these two key fragments were developed and demonstrated to synthesize kilogram quantities. Key steps involve a two-step thiophenol alkylation/cyclization protocol to synthesize 2 in a convergent manner. A difficult Pd-mediated coupling to produce 3 was replaced with a more scalable stepwise imidazole synthesis. Key rationale for the new routes are discussed.