2-(1-benzyl-5-fluoro-2-oxoindolin-3-ylidene)malononitrile | 876564-71-5

• 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: 2-(1-benzyl-5-fluoro-2-oxoindolin-3-ylidene)malononitrile
• 英文别名: 2-(1-Benzyl-5-fluoro-2-oxoindol-3-ylidene)propanedinitrile
• CAS: 876564-71-5
• 化学式: C₁₈H₁₀FN₃O
• 分子量: 303.295
• InChiKey: XAVVRJWHVRRPNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  67.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(1-benzyl-5-fluoro-2-oxoindolin-3-ylidene)malononitrile 、 白杨素 以 甲醇 为溶剂， 反应 8.0h， 生成 2′-amino-1-benzyl-5-fluoro-5′-hydroxy-2,6′-dioxo-8′-phenyl-6′Hspiro[indoline-3,4′- pyrano[3,2-g]chromene]-3′‑carbonitrile
  参考文献：
  名称：

  Design, synthesis and evaluation of structurally diverse chrysin-chromene-spirooxindole hybrids as anticancer agents

  摘要：

  A series of structurally diverse chrysin-chromene-spirooxindole hybrids were designed, synthesized via a Knoevenagel/Michael/cyclization of chrysin and isatylidene malononitrile derivatives through utilizing a hybrid pharmacophore approach. The newly synthesized compounds were evaluated for their in vitro anticancer activity, and most of the compounds showed stronger anti-proliferative activity than parent compound chrysin. In particular, compound 3e had the highest cytotoxicity towards A549 cells (IC50 = 3.15 +/- 0.51 mu M), and had better selectivity in A549 cells and normal MRC-5 cells. Furthermore, compound 3e could significantly inhibit the proliferation and migration of A549 cells in a dose-dependent manner, as well as induce the apoptosis possibly through mitochondria-mediated caspase-3/8/9 activation and multi-target co-regulation of the p53 signaling pathway. Thus, our results provide in vitro evidence that compound 3e may be a potential candidate for the development of new anti-tumour drugs.

  DOI：

  10.1016/j.bmc.2019.115109
• 作为产物：
  描述：

  溴甲苯 在 哌啶 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 1.0h， 生成 2-(1-benzyl-5-fluoro-2-oxoindolin-3-ylidene)malononitrile
  参考文献：
  名称：

  Triphenylphosphine-Catalyzed [3+2] Cycloaddition of Allenoate and Active Olefins: Syntheses of Spirooxindole Derivatives

  摘要：

  通过三苯基膦催化的[3+2]环加成反应，成功合成了一系列螺旋化合物，反应物为活性亚甲基马隆腈和乙基2,3-丁二烯酸酯。细致的研究表明，该方法具有较高的区域选择性。产物呈现出螺氧吲哚骨架，这是一种在许多自然产物和药效活性化合物中常见的结构特征。

  DOI：

  10.1055/s-0030-1261188

文献信息

• Multicomponent Reaction to Construct Spirocyclic Oxindoles with a Michael (Triple Michael)/Cyclization Cascade Sequence as the Key Step
  作者：Jian Li、Ning Wang、Chunju Li、Xueshun Jia

  DOI：10.1002/chem.201104071

  日期：2012.7.27

  new strategy to access highly unusual tricyclic oxindoles. From a synthetic point of view, this protocol is very interesting considering the high level of complexity reached in one step. The mechanism is thought to proceed by a triple Michael/cyclization process by using allenoate as a three carbon atom component (3 C). Furthermore, multicomponent reaction with γ‐substituted allenoate also results in

  公开了具有容易获得的异氰酸酯，脲基酸酯和异亚丙基丙二腈的多组分环加成物。该反应不需要任何催化剂的帮助，使得能够以优异的区域选择性有效地合成螺环恶吲哚。还充分探讨了与2,3-丁二烯酸乙酯和各种结构不同的α-和γ-取代的烯醇酸酯的反应。值得注意的是，我们已经表明，通常的三组分过程可以在存在水的情况下进一步发展为史无前例的四组分环加成反应，这提供了一种新的策略来获得高度不寻常的三环羟吲哚。从综合的角度来看，考虑到一步就可以达到很高的复杂性，该协议非常有趣。该机理被认为是通过使用烯丙酸酯作为三个碳原子组分（3 C）通过三重迈克尔/环化过程进行的。此外，与γ-取代的脲基甲酸酯的多组分反应也导致非常有趣的转化。在这种情况下，总是观察到异亚丙基丙二腈的“CC”双键和脲基酸酯的“CC”双键之一的不寻常断裂。
• Phosphine-Catalyzed Asymmetric Formal [4+2] Tandem Cyclization of Activated Dienes with Isatylidenemalononitriles: Enantioselective Synthesis of Multistereogenic Spirocyclic Oxindoles
  作者：Fang-Le Hu、Yin Wei、Min Shi

  DOI：10.1002/adsc.201301070

  日期：2014.3.10

  enantioselective formal [4+2] tandem cyclizations between isatylidenemalononitriles and activated dienes catalyzed by bifunctional chiral phosphine catalysts have been developed, yielding multistereogenic spirocyclic oxindoles in high yields and excellent optical purity. This reaction is accomplished via a tandem Rauhut–Currier/Michael/Rauhut–Currier reaction sequence.

  已开发出双功能手性膦催化剂催化的异亚乙基丙二腈和活化的二烯之间的第一个高度对映选择性的正式[4 + 2]串联环化反应，可高收率和出色的光学纯度产生多立体异构螺环式吲哚。该反应是通过串联的Rauhut-Currier / Michael / Rauhut-Currier反应序列完成的。
• Efficient synthesis of functionalized spiro[indoline-3,4′-pyridines] and spiro[indene-2,4′-pyridines] <i>via</i> a three-component reaction
  作者：Jing Zhang、Jing Sun、Chao-Guo Yan

  DOI：10.1039/c5ra15139b

  日期：——

  and isatylidene malononitriles in dry acetonitrile at room temperature afforded polysubstituted spiro[indoline-3,4′-pyridines] in good yields and with high diastereoselectivity. Under similar reaction conditions, the corresponding functionalized spiro[indene-2,4′-pyridines] were also obtained from the three-component reactions containing 2-(1,3-dioxo-1H-inden-2(3H)-ylidene)malononitrile.

  室温下，α，β-不饱和N-芳基亚胺，乙炔二甲酸二甲酯（丙酸甲酯）和异亚丙基丙二腈在干燥的乙腈中的三组分反应提供了高收率和高非对映选择性的多取代螺[吲哚啉-3,4'-吡啶] 。在相似的反应条件下，还从含有2-（1,3-二氧代-1 H-茚满-2（3 H）-亚烷基的三组分反应中获得了相应的官能化螺[茚-2,4'-吡啶]丙二腈。
• Grinding assisted, column chromatography free decarboxylative carbon-carbon bond formation: Greener synthesis of 3, 3-disubstituted oxindoles
  作者：Jasneet Kaur、Anita Kumari、Swapandeep Singh Chimni

  DOI：10.1016/j.tet.2016.12.070

  日期：2017.2

  The decarboxylative carbon-carbon bond formation reaction of β-ketoacid derivatives with isatylidene malononitrile derivatives catalyzed by DBU afford adducts in excellent yield. The desired product can be easily isolated using simple filtration method without performing any column chromatography. The decarboxylative adduct was further subjected to reductive-cyclization to obtain biologically important

  DBU催化β-酮酸衍生物与异亚丙基丙二腈衍生物的脱羧碳-碳键形成反应，得到的加合物收率高。所需产物可以使用简单的过滤方法容易地分离，而无需进行任何柱色谱法。脱羧加合物进一步进行还原环化，以89％的产率获得生物学上重要的螺硫醇。
• Iron-catalyzed cross-dehydrogenative coupling of indolin-2-ones with active methylenes for direct carbon–carbon double bond formation
  作者：Zhi-Yu Tan、Ke-Xin Wu、Lu-Shan Huang、Run-Shi Wu、Zheng-Yu Du、Da-Zhen Xu

  DOI：10.1039/c9gc03639c

  日期：——

  The iron-catalyzed cross-dehydrogenative coupling (CDC) of C(sp3)–H/C(sp3)–H bonds to afford olefins by 4H elimination is described. This method employs air (molecular oxygen) as an ideal oxidant, and is performed under mild, ligand-free and base-free conditions. H2O is the only byproduct. Good tolerance of functional groups and high yields have also been achieved. Preliminary mechanistic investigations

  描述了铁催化的C（sp 3）–H / C（sp 3）–H键的交叉脱氢偶联（CDC），可通过4H消除得到烯烃。该方法使用空气（分子氧）作为理想的氧化剂，并且在温和，无配体和无碱的条件下进行。H 2 O是唯一的副产物。还获得了对官能团的良好耐受性和高产率。初步的机械研究表明，目前的转变涉及一个根本过程。