2-(1-benzyl-5-methyl-2-oxoindolin-3-ylidene)malononitrile | 1311318-52-1

• 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-methyl-2-oxoindolin-3-ylidene)malononitrile
• 英文别名: 2-(1-Benzyl-5-methyl-2-oxoindol-3-ylidene)propanedinitrile
• CAS: 1311318-52-1
• 化学式: C₁₉H₁₃N₃O
• 分子量: 299.332
• InChiKey: KKHGDCGJVSQEFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  67.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(1-benzyl-5-methyl-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′-hydroxy-5-methyl-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 sodium carbonate 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 27.0h， 生成 2-(1-benzyl-5-methyl-2-oxoindolin-3-ylidene)malononitrile
  参考文献：
  名称：

  通过连续有机催化迈克尔-多米诺迈克尔/羟醛反应立体选择性合成螺十氢萘吲哚衍生物

  摘要：

  已经开发出一种高度立体选择性的方法，用于合成具有五个连续立体中心（包括两个四取代碳）的螺多环羟吲哚。在基于吡咯烷的有机催化剂和 DBU 进行的连续有机催化下，优化了高度原子经济的 Michael-domino Michael/aldol 反应序列，产生了具有优异立体选择性的各种功能化的螺十氢萘吲哚（>99:1 dr，高达 92%） ee）。

  DOI：

  10.1021/acs.joc.2c01046

文献信息

• 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。
• A Three-Component Condensation for the Construction of the Spiro[indoline-3,3′-piperidin]-2-one Skeleton
  作者：Hai-Bin Yang、Xiao-Yang Guan、Yin Wei、Min Shi

  DOI：10.1002/ejoc.201200185

  日期：2012.5

  Treatment of pyridine and dimethyl acetylenedicarboxylate derivatives with N-substituted isatylidene derivatives resulted in three-component condensations, affording 1′,9a′-dihydrospiro[indoline-3,2-quinolizin]-2-one derivatives in high yields and with good diastereoselectivities through 1,4-dipolar cycloadditions.

  用 N-取代的异亚甲基衍生物处理吡啶和二甲基乙炔二羧酸衍生物导致三组分缩合，得到 1',9a'-二氢螺[indoline-3,2-quinolizin]-2-one 衍生物，通过1,4-偶极环加成。
• Three-Component Condensation for the Construction of Novel Spirooxindoles
  作者：Chun Cai、Fei Ji、Mu Sun、Mei-fang Lv、Wen-bin Yi

  DOI：10.1055/s-0032-1316836

  日期：——

  using a copper azide–alkyne cycloaddition­ (CuAAC) reaction. A new route for the synthesis of novel spirooxindoles from isocyanides, dialkyl acetylenedicarboxylates, and N-substituted isatylidene derivatives through [3+2] cycloaddition has been developed. This method has several advantages, such as high regioselectivity, high yields, readily available starting materials, and one-pot operations. The

  摘要 已开发出一种新的途径，可以通过[3 + 2]环加成反应从异氰酸酯，乙炔二羧酸二烷基酯和N-取代的异亚戊二烯衍生物合成新型螺硫辛多。该方法具有几个优点，例如高区域选择性，高收率，易于获得的起始原料和一锅操作。合成的含炔烃的螺硫醇也可用于通过叠氮化铜-炔烃环加成（CuAAC）反应选择性合成含三唑的螺环化合物。 已开发出一种新的途径，可以通过[3 + 2]环加成反应从异氰酸酯，乙炔二羧酸二烷基酯和N-取代的异亚戊二烯衍生物合成新型螺硫辛多。该方法具有几个优点，例如高区域选择性，高收率，易于获得的起始原料和一锅操作。合成的含炔烃的螺硫醇也可用于通过叠氮化铜-炔烃环加成（CuAAC）反应选择性合成含三唑的螺环化合物。