2-[5-(4-methanesulfonyl-piperazin-1-yl-methyl)-2-nitrophenyl]-1-(2-methoxyquinolin-3-yl)-ethanol | 796854-51-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-[5-(4-methanesulfonyl-piperazin-1-yl-methyl)-2-nitrophenyl]-1-(2-methoxyquinolin-3-yl)-ethanol
• 英文别名: 2-[5-(4-methanesulfonylpiperazin-1-ylmethyl)-2-nitrophenyl]-1-(2-methoxyquinolin-3-yl)ethanol；2-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-2-nitro-phenyl]-1-(2-methoxy-quinolin-3-yl)-ethanol；1-(2-methoxyquinolin-3-yl)-2-[5-[(4-methylsulfonylpiperazin-1-yl)methyl]-2-nitrophenyl]ethanol
• CAS: 796854-51-8
• 化学式: C₂₄H₂₈N₄O₆S
• 分子量: 500.576
• InChiKey: PJLMBUDUPZOQRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  137
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-[5-(4-methanesulfonyl-piperazin-1-yl-methyl)-2-nitrophenyl]-1-(2-methoxyquinolin-3-yl)-ethanol 在 三氟乙酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以78%的产率得到trans-3-{2-[5-(4-methanesulfonylpiperazin-1-ylmethyl)-2-nitrophenyl]vinyl}-2-methoxyquinoline
  参考文献：
  名称：

  [EN] SUBSTITUTED INDOLES AND A PROCESS FOR PREPARING SUBSTITUTED INDOLES
  [FR] INDOLES SUBSTITUES ET PROCEDE DE PREPARATION D'INDOLES SUBSTITUES

  摘要：

  公开号：

  WO2005000804A3
• 作为产物：
  描述：

  1-[(4-硝基苯基)甲基]哌嗪 在 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 醋酸异丙酯 为溶剂， 反应 4.5h， 生成 2-[5-(4-methanesulfonyl-piperazin-1-yl-methyl)-2-nitrophenyl]-1-(2-methoxyquinolin-3-yl)-ethanol
  参考文献：
  名称：

  Synthesis of 5-Substituted-1H-indol-2-yl-1H-quinolin-2-ones:  A Novel Class of KDR Kinase Inhibitors

  摘要：

  A number of approaches for the synthesis of the 1H-indol-2-yl-1H-quinolin-2-one ring system found in the potent and selective KDR kinase inhibitor 1 are described. The preparation and reaction of trimethylsilylnitrobenzene 26 with 2-methoxy-3-quinolinecarboxaldehyde 28 afforded alcohol 30, which was the key intermediate for the preparation of the target compounds. Conversion of alcohol 30 to either nitroketone 36 or nitrostyrene 45 set the stage for reductive cyclization and the formation of indole 25. The quinolin-2-one functionality was unmasked in the last step to provide compound 1 in 56-60% overall yield from readily available starting materials.

  DOI：

  10.1021/jo0480545

文献信息

• Synthesis of Novel KDR Kinase Inhibitors through Catalytic Reductive Cyclization of <i>o</i>-Nitrobenzylcarbonyl Compounds
  作者：Audrey Wong、Jeffrey T. Kuethe、Ian W. Davies、David L. Hughes

  DOI：10.1021/jo048843m

  日期：2004.10.1

  through the Swern-type oxidation of readily accessible phenethanol analogues. Reductive cyclization of o-nitrobenzylcarbonyl 3 using catalytic Raney nickel gives 1H-indol-2-yl-1H-quinoline 2 in 95% yield. Hydrolysis of 2 affords the KDR kinase inhibitor 1 in quantitative yield. The examination of the reductive cyclization reaction and optimization of conditions is described.

  通过容易获得的苯乙醇类似物的Swern型氧化证明了邻硝基苄基羰基化合物的有效合成。使用催化阮内镍对邻硝基苄基羰基3进行还原环化，可得到1 H-吲哚-2-基-1 H-喹啉2，产率为95％。2的水解可定量提供KDR激酶抑制剂1。描述了还原环化反应的检查和条件的优化。
• Substituted indoles and a process for preparing substituted indoles
  申请人：Davies W Ian

  公开号：US20070054921A1

  公开（公告）日：2007-03-08

  The instant invention is directed to novel compounds of Formulae (I) and (II), as wells a process for preparing compounds of Formula (II). The process comprises a palladium-catalyzed reductive cyclization of a compound of Formula (I) to produce a compound of Formula (II).

  本发明涉及式（I）和（II）的新化合物，以及制备式（II）的方法。该方法包括通过钯催化的还原环化反应将式（I）的化合物还原为式（II）的化合物。
• [EN] SUBSTITUTED INDOLES AND A PROCESS FOR PREPARING SUBSTITUTED INDOLES<br/>[FR] INDOLES SUBSTITUES ET PROCEDE DE PREPARATION D'INDOLES SUBSTITUES
  申请人：MERCK & CO INC

  公开号：WO2005000804A3

  公开（公告）日：2005-08-04
• Synthesis of 5-Substituted-1<i>H</i>-indol-2-yl-1<i>H</i>-quinolin-2-ones:  A Novel Class of KDR Kinase Inhibitors
  作者：Jeffrey T. Kuethe、Audrey Wong、Chuanxing Qu、Jacqueline Smitrovich、Ian W. Davies、David L. Hughes

  DOI：10.1021/jo0480545

  日期：2005.4.1

  A number of approaches for the synthesis of the 1H-indol-2-yl-1H-quinolin-2-one ring system found in the potent and selective KDR kinase inhibitor 1 are described. The preparation and reaction of trimethylsilylnitrobenzene 26 with 2-methoxy-3-quinolinecarboxaldehyde 28 afforded alcohol 30, which was the key intermediate for the preparation of the target compounds. Conversion of alcohol 30 to either nitroketone 36 or nitrostyrene 45 set the stage for reductive cyclization and the formation of indole 25. The quinolin-2-one functionality was unmasked in the last step to provide compound 1 in 56-60% overall yield from readily available starting materials.