Imidazol-1-yl-(6-methoxy-2-methyl-1-benzothiophen-3-yl)methanone | 929115-69-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: Imidazol-1-yl-(6-methoxy-2-methyl-1-benzothiophen-3-yl)methanone
• 英文别名: imidazol-1-yl-(6-methoxy-2-methyl-1-benzothiophen-3-yl)methanone
• CAS: 929115-69-5
• 化学式: C₁₄H₁₂N₂O₂S
• 分子量: 272.327
• InChiKey: CWZAIUHWXOLRST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  3-(3-methoxyphenylthio)-2-oxobutanoic acid 在 硫酸 作用下， 以 四氢呋喃 、 正庚烷 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 Imidazol-1-yl-(6-methoxy-2-methyl-1-benzothiophen-3-yl)methanone
  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

• WO2007/26221
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] IMPROVED METHODS FOR PREPARING BENZOFUSED HETEROARYL AMIDE DERIVATIVES OF THIENOPYRIDINES<br/>[FR] PROCEDE AMELIORES D'ELABORATION DE DERIVES D'HETEROARYL AMIDE BENZOCONDENSES DE THIENOPYRIDINES
  申请人：PFIZER

  公开号：WO2007026221A2

  公开（公告）日：2007-03-08

  [EN] The invention relates to methods for preparing compounds of formulae (I) and (XI): or pharmaceutically acceptable salts or solvates thereof. Compounds of the formula (I) and (XI) Fare useful as anti-angiogenesis agents and as agents for modulating and/or inhibiting the activity of protein kinases, thus providing treatments for cancer or other diseases associated with cellular proliferation mediated by protein kinases.
  [FR] L'invention concerne des procédés d'élaboration de composés représentés par les formules (I) et (XI), ou de sels ou solvates pharmaceutiquement acceptables de ces composés. Les composés représentés par la formule (I) ou (XI) sont utiles comme agents anti-angiogéniques et comme agents destinés à moduler et/ou à inhiber l'activité de protéines kinases, et permettent ainsi de traiter le cancer ou d'autres maladies associées à la prolifération cellulaire impliquant les protéines kinases.
• 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.