1-(methylsulfonyl)-4-{4-nitro-3-[(trimethylsilyl)methyl]benzyl}piperazine | 615552-65-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(methylsulfonyl)-4-{4-nitro-3-[(trimethylsilyl)methyl]benzyl}piperazine
• 英文别名: 1-methanesulfonyl-4-(4-nitro-3-trimethylsilanylmethylbenzyl)piperazine；1-methanesulfonyl-4-(4-nitro-3-trimethylsilylmethyl-benzyl)piperazine；1-methanesulfonyl-4-(4-nitro-3-trimethylsilanylmethyl-benzyl)-piperazine；Trimethyl-[[5-[(4-methylsulfonylpiperazin-1-yl)methyl]-2-nitrophenyl]methyl]silane
• CAS: 615552-65-3
• 化学式: C₁₆H₂₇N₃O₄SSi
• 分子量: 385.56
• InChiKey: FHLLWFXSUNVRPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.09
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  94.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(methylsulfonyl)-4-{4-nitro-3-[(trimethylsilyl)methyl]benzyl}piperazine 在 四丁基氟化铵 、 三氟乙酸 作用下， 以 醋酸异丙酯 为溶剂， 反应 3.5h， 生成 trans-3-{2-[5-(4-methanesulfonylpiperazin-1-ylmethyl)-2-nitrophenyl]vinyl}-2-methoxyquinoline
  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
• 作为产物：
  描述：

  1-[(4-硝基苯基)甲基]哌嗪 在 三乙胺 作用下， 以 四氢呋喃 、 醋酸异丙酯 为溶剂， 反应 4.0h， 生成 1-(methylsulfonyl)-4-{4-nitro-3-[(trimethylsilyl)methyl]benzyl}piperazine
  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

• Effective Strategy for the Preparation of Indolocarbazole Aglycons and Glycosides:  Total Synthesis of Tjipanazoles B, D, E, and I
  作者：Jeffrey T. Kuethe、Audrey Wong、Ian W. Davies

  DOI：10.1021/ol035418r

  日期：2003.10.1

  [reaction: see text] An effective strategy has been developed for the rapid and efficient preparation of ortho-nitrostyrenes, which can be converted to unsymmetrical 2,2'-biindoles. A unique condensation of these 2,2'-biindoles with (dimethylamino)-acetaldehyde diethyl acetal affords the indolocarbazole ring system of the tjipanazole aglycon alkaloids in three synthetic steps and good to excellent

  [反应：见正文]已经开发出一种有效的策略，用于快速高效地制备邻硝基苯乙烯，该邻硝基苯乙烯可以转化为不对称的2,2'-双吲哚。这些2,2'-联吲哚与（二甲基氨基）-乙醛二乙基缩醛的独特缩合可在三个合成步骤中获得替潘唑苷元生物碱的吲哚并咔唑环系，并具有优异的总收率。还讨论了吉潘唑糖苷生物碱B和E的第一个全合成。
• 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。
• [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.