2-methoxy-3-(5-{[4-(methylsulfonyl)-1-piperazinyl]-methyl}-1H-indol-2-yl)-quinoline | 796854-61-0

• 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-methoxy-3-(5-{[4-(methylsulfonyl)-1-piperazinyl]-methyl}-1H-indol-2-yl)-quinoline
• 英文别名: 2-methoxy-3-[5-[[4-(methylsulfonyl)-1-piperazinyl]methyl]-1H-indol-2-yl]-quinoline；2-methoxy-3-[5-[[4-(methylsulfonyl)-1-piperazinyl]methyl]-1H-indol-2-yl]quinoline；3-[5-(4-methanesulfonylpiperazin-1-ylmethyl)-1H-indol-2-yl]-2-methoxyquinoline；3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-1H-indol-2-yl]-2-methoxy-quinoline；2-methoxy-3-[5-[(4-methylsulfonylpiperazin-1-yl)methyl]-1H-indol-2-yl]quinoline
• CAS: 796854-61-0
• 化学式: C₂₄H₂₆N₄O₃S
• 分子量: 450.561
• InChiKey: WIUNQPYPBHKJKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  86.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-methoxy-3-(5-{[4-(methylsulfonyl)-1-piperazinyl]-methyl}-1H-indol-2-yl)-quinoline 在 盐酸 作用下， 以 甲醇 为溶剂， 以95%的产率得到3-[5-(4-methanesulfonylpiperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one hydrochloride
  参考文献：
  名称：

  以Pd催化串联CN /铃木偶联为关键步骤的KDR激酶抑制剂的高效合成

  摘要：

  包含吲哚-2-基喹啉-2-酮结构的四个有效的KDR激酶抑制剂家族正在利用Pd催化的串联CN和C偶联序列。

  DOI：

  10.1021/jo062228w
• 作为产物：
  描述：

  1-[(4-硝基苯基)甲基]哌嗪 在 palladium diacetate 、 ammonium heptamolybdate 、 palladium on activated charcoal palladium diacetate 、 sodium perborate 、 一氧化碳 、 氢气 、 溶剂黄146 、 三乙胺 、 三苯基膦 、 三(邻甲基苯基)磷 、 potassium bromide 作用下， 以 醋酸异丙酯 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 20.0~100.0 ℃ 、413.68 kPa 条件下， 反应 31.5h， 生成 2-methoxy-3-(5-{[4-(methylsulfonyl)-1-piperazinyl]-methyl}-1H-indol-2-yl)-quinoline
  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。
• Screening Methods
  申请人：Lautens Mark

  公开号：US20080039625A1

  公开（公告）日：2008-02-14

  Disclosed are processes for the preparation of 2-substituted indole compounds wherein the 2-substituent comprises an R 4 group, wherein R 4 is selected from the group consisting of monocyclic aromatic, polycyclic aromatic, monocyclic heteroaromatic, polycyclic heteroaromatic, 1° alkyl, and alkenyl, all of which are optionally substituted at one or more substitutable positions with one or more suitable substituents, and wherein R 4 is bonded to the 2-position of the indole ring via a C—C bond; the process comprising reacting an orthogem-dihalovinylaniline compound of the formula (I): wherein Halo comprises Br, Cl, or I; each of the one or more R 1 is independently selected from the group consisting of H, fluoro, lower alkyl, lower alkenyl, lower alkoxy, aryloxy, lower haloalkyl, lower alkenyl, —C(O)O-lower alkyl, monocyclic or polycyclic aryl or heteroaryl moiety, or R 1 is an alkenyl group bonded so to as to form a 4- to 20-membered fused monocycle or polycyclic ring with the indole ring; all of which are optionally substituted with one or more suitable substituents at one or more substitutable positions; R 2 comprises H, alkyl, cycloalkyl, aryl, heteroaryl, aryl-loweralkyl-, or heteroaryl-loweralkyl-, all of which are optionally substituted at one or more substitutable positions with one or more suitable substituents; R 3 comprises H, alkyl, haloalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocycle, aryl-(C 1-6 )alkyl-, or heteroaryl-loweralkyl-, all of which are optionally substituted at one or more substitutable positions with one or more suitable substituents; with an organoboron reagent selected from the group consisting of a boronic ester of R 4 , a boronic acid of R 4 , a boronic acid anhydride of R 4 , a trialkylborane of R 4 and a 9-BBN derivative of R 4 ; in the presence of a base, a palladium metal pre-catalyst and a ligand under reaction conditions effective to form the 2-substituted indole compound. Also disclosed are processes for the preparation of ortho-gem-dihalovinylaniline compounds. Novel compounds prepared by the processes and novel uses of the compounds are likewise disclosed.

  本发明涉及制备2-取代吲哚化合物的方法，其中2-取代基包括R4基团，其中R4从单环芳香族、多环芳香族、单环杂芳族、多环杂芳族、1°烷基和烯基中选择，所有这些基团都可以在一个或多个可替换的位置上用一个或多个适当的取代基替换，并且其中R4通过C-C键与吲哚环的2-位置结合；该方法包括将式（I）的正交二卤代乙烯基苯胺化合物与来自以下组的有机硼试剂反应：其中Halo包括Br、Cl或I；其中一个或多个R1各自独立地选择自H、氟、低烷基、低烯基、低烷氧基、芳氧基、低卤代烷基、低烯基、-C（O）O-低烷基、单环或多环芳基或杂芳基基团，或者R1是一个烯基团，通过与吲哚环形成一个4到20个成员的融合的单环或多环环，所有这些基团都可以在一个或多个可替换的位置上用一个或多个适当的取代基替换；R2包括H、烷基、环烷基、芳基、杂芳基、芳基-低烷基-或杂芳基-低烷基-，所有这些基团都可以在一个或多个可替换的位置上用一个或多个适当的取代基替换；R3包括H、烷基、卤代烷基、烯基、炔基、芳基、杂芳基、环烷基、杂环、芳基-(C1-6)烷基-或杂芳基-低烷基-，所有这些基团都可以在一个或多个可替换的位置上用一个或多个适当的取代基替换；在碱、钯金属预催化剂和配体存在下，以有效的反应条件形成2-取代吲哚化合物。本发明还涉及制备正交二卤代乙烯基苯胺化合物的方法。本发明还涉及通过上述方法制备的新化合物以及化合物的新用途。
• 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。
• A highly active catalyst for the reductive cyclization of ortho-nitrostyrenes under mild conditions
  作者：Ian W. Davies、Jacqueline H. Smitrovich、Rick Sidler、Chuanxing Qu、Venita Gresham、Charles Bazaral

  DOI：10.1016/j.tet.2005.03.142

  日期：2005.6

  A mild and efficient method for the palladium-Catalyzed reductive Cyclization of ortho-nitrostyrenes to afford indoles is reported. \Treatment of ortho-nitrostyrenes with 0.1 mol% palladium (II) trifluoracetate [Pd(TFA)(2)] and 0.7 mol% 3.4,7,8-tetramethyl-1,10-phenanthroline (tm-phen) in DMF at 15 psig CO and 80 degrees C afforded indoles in good to excellent yields. When the reaction was conducted in toluene. the corresponding N-hydroxyindole was isolated. A mechanism that accounts for the formation of N-hydroxyindole is proposed. (c) 2005 Elsevier Ltd. All rights reserved.
• WO2006/47888
  申请人：——

  公开号：——

  公开（公告）日：——