6-甲氧基-N,2-二甲基-1-苯并噻吩-3-甲酰胺 | 638216-86-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 中文名称: 6-甲氧基-N,2-二甲基-1-苯并噻吩-3-甲酰胺
• 英文名称: 6-methoxy-N,2-dimethylbenzo[b]thiophene-3-carboxamide
• 英文别名: 6-methoxy-2-methylbenzo[b]thiophene-3-carboxylic acid methylamide；6-Methoxy-N,2-dimethyl-1-benzothiophene-3-carboxamide
• CAS: 638216-86-1
• 化学式: C₁₂H₁₃NO₂S
• 分子量: 235.307
• InChiKey: PDXWKGQTDMFWAL-UHFFFAOYSA-N

物化性质

• 熔点：
  157.9-159.0 °C
• 沸点：
  424.1±45.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  66.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-甲氧基-N,2-二甲基-1-苯并噻吩-3-甲酰胺 在 caesium carbonate 、 DL-蛋氨酸 作用下， 以 甲烷磺酸 、 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 46.5h， 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 、 水 为溶剂， 反应 7.5h， 生成 6-甲氧基-N,2-二甲基-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

• [EN] BENZOFUSED HETEROARYL AMIDE DERIVATIVES OF THIENOPYRIDINES USEFUL AS THERAPEUTIC AGENTS, PHARMACEUTICAL COMPOSITIONS INCLUDING THE SAME, AND METHODS FOR THEIR USE<br/>[FR] DERIVES D'AMIDE HETEROARYLE BENZOCONDENSE DE THIENOPYRIDINES UTILISEES EN TANT QU'AGENTS THERAPEUTIQUES, COMPOSITIONS PHARMACEUTIQUES LES CONTENANT ET PROCEDES D'UTILISATION ASSOCIES
  申请人：PFIZER

  公开号：WO2003106462A1

  公开（公告）日：2003-12-24

  The invention relates to compounds represented by the formula I and to prodrugs or metabolites thereof, or pharmaceutically acceptable salts or solvates of said compounds, said prodrugs, and said metabolites, wherein Z, Y, R11 and R14, R15, R16, and R17 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula I and to methods of treating hyperproliferative disorders in a mammal by administering the compounds of formula I.

  该发明涉及由公式I表示的化合物，以及这些化合物的前药或代谢物，或者这些化合物的药用可接受的盐或溶剂化合物，所述前药和代谢物，其中Z、Y、R11和R14、R15、R16和R17如本文所定义。该发明还涉及含有公式I化合物的药物组合物，以及通过给予公式I化合物来治疗哺乳动物的增殖过度性疾病的方法。
• Benzofused heterozryl amide derivatives of thienopyridines useful as therapeutic agents, pharmaceutical compositions including the same, and methods for their use
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：US20040009965A1

  公开（公告）日：2004-01-15

  The invention relates to compounds represented by the formula I 1 and to prodrugs or metabolites thereof, or pharmaceutically acceptable salts or solvates of said compounds, said prodrugs, and said metabolites, wherein Z, Y, R 11 and R 14 , R 15 , R 16 , and R 17 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula I and to methods of treating hyperproliferative disorders in a mammal by administering the compounds of formula I.

  这项发明涉及由公式I1表示的化合物，以及这些化合物的前药或代谢物，或这些化合物的药用可接受的盐或溶剂，所述前药和所述代谢物，其中Z、Y、R11和R14、R15、R16和R17如本文所定义。该发明还涉及含有公式I化合物的药物组合物，以及通过给哺乳动物施用公式I化合物来治疗过度增殖性疾病的方法。
• WO2007/26221
  申请人：——

  公开号：——

  公开（公告）日：——
• BENZOFUSED HETEROARYL AMIDE DERIVATIVES OF THIENOPYRIDINES USEFUL AS THERAPEUTIC AGENTS, PHARMACEUTICAL COMPOSITIONS INCLUDING THE SAME, AND METHODS FOR THEIR USE
  申请人：PFIZER INC.

  公开号：EP1515975A1

  公开（公告）日：2005-03-23
• US6869962B2
  申请人：——

  公开号：US6869962B2

  公开（公告）日：2005-03-22