3-(3-methoxyphenylthio)-2-oxobutanoic acid | 881688-69-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(3-methoxyphenylthio)-2-oxobutanoic acid
• 英文别名: 3-(3-methoxyphenylthio)2-ketobutyric acid；3-[(3-Methoxyphenyl)sulfanyl]-2-oxobutanoic acid；3-(3-methoxyphenyl)sulfanyl-2-oxobutanoic acid
• CAS: 881688-69-3
• 化学式: C₁₁H₁₂O₄S
• 分子量: 240.28
• InChiKey: VKLORHYRGDAUMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  88.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  3-溴-2-氧代丁酸 、 3-甲氧基苯硫酚 在 potassium carbonate 、 盐酸 作用下， 以 1,2-二氯乙烷 、 丙酮 、 水 为溶剂， 反应 0.52h， 生成 3-(3-methoxyphenylthio)-2-oxobutanoic acid
  参考文献：
  名称：

  WO2007/26221

  摘要：

  公开号：

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.