(E)-6-chloro-3-(3-chloro-2-fluorobenzylidene)-N-acetylindolin-2-one | 1422199-59-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (E)-6-chloro-3-(3-chloro-2-fluorobenzylidene)-N-acetylindolin-2-one
• 英文别名: (3E)-1-acetyl-6-chloro-3-[(3-chloro-2-fluorophenyl)methylidene]indol-2-one
• CAS: 1422199-59-4
• 化学式: C₁₇H₁₀Cl₂FNO₂
• 分子量: 350.176
• InChiKey: KVESKJMPUOUEOD-NTUHNPAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-6-chloro-3-(3-chloro-2-fluorobenzylidene)-N-acetylindolin-2-one 在 三甲基铝 、 二甲基苯基磷 作用下， 以 甲苯 为溶剂， 反应 46.5h， 生成 6'-chloro-N-(2-morpholinoethyl)-2'-oxo-2-(3-chloro-2-fluorophenyl)-5-neopentylspiro[cyclopent[3]ene-1,3'-indoline]-3-carboxamide
  参考文献：
  名称：

  Phosphine-Catalyzed Synthesis of 3,3-Spirocyclopenteneoxindoles from γ-Substituted Allenoates: Systematic Studies and Targeted Applications

  摘要：

  The phosphine-promoted [3 + 2] cyclizations between gamma-substituted allenoates and arylideneoxindoles have been applied to the stereoselective synthesis of spiro(cyclopentene)oxindoles with trisubstituted cyclopentene units. It has been demonstrated that PPh3 operates a very efficient control of the relative stereochemistry of the three stereogenic centers of the final spiranic products. Focused experiments have been carried out then so as to access carbocyclic analogues of an important series of anticancer agents inhibiting MDM2-p53 interactions.

  DOI：

  10.1021/jo302460d
• 作为产物：
  描述：

  3-氯-2-氟苯甲醛 在 哌啶 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 14.0h， 生成 (E)-6-chloro-3-(3-chloro-2-fluorobenzylidene)-N-acetylindolin-2-one
  参考文献：
  名称：

  Phosphine-Catalyzed Synthesis of 3,3-Spirocyclopenteneoxindoles from γ-Substituted Allenoates: Systematic Studies and Targeted Applications

  摘要：

  The phosphine-promoted [3 + 2] cyclizations between gamma-substituted allenoates and arylideneoxindoles have been applied to the stereoselective synthesis of spiro(cyclopentene)oxindoles with trisubstituted cyclopentene units. It has been demonstrated that PPh3 operates a very efficient control of the relative stereochemistry of the three stereogenic centers of the final spiranic products. Focused experiments have been carried out then so as to access carbocyclic analogues of an important series of anticancer agents inhibiting MDM2-p53 interactions.

  DOI：

  10.1021/jo302460d

文献信息

• Synthesis of 3,3′-Spirocyclic Oxindoles via Phosphine Catalyzed [4 + 2] Cyclizations
  作者：Maxime Gicquel、Catherine Gomez、Pascal Retailleau、Arnaud Voituriez、Angela Marinetti

  DOI：10.1021/ol401798w

  日期：2013.8.2

  Triphenylphosphine promoted reactions between 3-arylideneoxindoles and (delta-aryl-substituted penta-2,3-dienoates afford an unprecedented access to spirocyclic oxindoles with functionalized six-membered rings. In these new [4 + 2] cyclization processes, the allenoates operate as the four-carbon synthons, thanks to the involvement of the substituted (delta-carbons. These reactions give excellent control of the relative stereochemistry of the three stereogenic centers. The stereochemistry of the final product has been ascertained by X-ray diffraction studies.
• Inhibition of p53-Murine Double Minute 2 (MDM2) Interactions with 3,3′-Spirocyclopentene Oxindole Derivatives
  作者：Maxime Gicquel、Catherine Gomez、Maria Concepcion Garcia Alvarez、Olivier Pamlard、Vincent Guérineau、Eric Jacquet、Jérôme Bignon、Arnaud Voituriez、Angela Marinetti

  DOI：10.1021/acs.jmedchem.8b01137

  日期：2018.10.25

  3,3'-Spirocyclopentene oxindoles structurally related to Wang's spiropyrrolidine oxindoles have been highlighted as a new class of antiproliferative agents against cancer cell lines with wild-type p53 status (IC50 up to 0.96 mu M on SJSA-1 and 2.9 mu M in HCT116 p53-wt). Inhibition of the MDM2-p53 interactions has been demonstrated through in vitro HTRF assays (IC50 up to 3.1 nM), while Western blot analysis showed activation of p53 selectively in HCT116 cancer cell lines with wild-type p53.
• Phosphine-Catalyzed Synthesis of 3,3-Spirocyclopenteneoxindoles from γ-Substituted Allenoates: Systematic Studies and Targeted Applications
  作者：Catherine Gomez、Maxime Gicquel、Jean-Christophe Carry、Laurent Schio、Pascal Retailleau、Arnaud Voituriez、Angela Marinetti

  DOI：10.1021/jo302460d

  日期：2013.2.15

  The phosphine-promoted [3 + 2] cyclizations between gamma-substituted allenoates and arylideneoxindoles have been applied to the stereoselective synthesis of spiro(cyclopentene)oxindoles with trisubstituted cyclopentene units. It has been demonstrated that PPh3 operates a very efficient control of the relative stereochemistry of the three stereogenic centers of the final spiranic products. Focused experiments have been carried out then so as to access carbocyclic analogues of an important series of anticancer agents inhibiting MDM2-p53 interactions.