(N-methyl-5-methoxy-2-oxo-3-indolindine)malononitrile | 133550-55-7

• 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: (N-methyl-5-methoxy-2-oxo-3-indolindine)malononitrile
• 英文别名: 2-(1-methyl-5-methoxy-2-oxoindolin-3-ylidene)malononitrile；2-(5-Methoxy-1-methyl-2-oxoindol-3-ylidene)propanedinitrile
• CAS: 133550-55-7
• 化学式: C₁₃H₉N₃O₂
• 分子量: 239.233
• InChiKey: OCAIUGBNGFVRJT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  77.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (N-methyl-5-methoxy-2-oxo-3-indolindine)malononitrile 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以46%的产率得到(N-methyl-5-hydroxy-2-oxo-3-indolinidene)malononitrile
  参考文献：
  名称：

  Tyrphostins. II. Heterocyclic and .alpha.-substituted benzylidenemalononitrile tyrphostins as potent inhibitors of EGF receptor and ErbB2/neu tyrosine kinases

  摘要：

  We have previously described a novel series of low molecular weight protein tyrosine kinase inhibitors which we named tyrphostins. The characteristic active pharmacophore of these compounds was the hydroxy-cis-benzylidenemalononitrile moiety. In this article we describe three novel groups of tyrphostins: (i) one group has the phenolic moiety of the cis-benzylidenemalononitrile replaced either with other substituted benzenes or with heteroaromatic rings, (ii) another is a series of conformationally constrained derivatives of hydroxy-cis-benzylidenemalononitriles in which the malononitrile moiety is fixed relative to the aromatic ring, and (iii) two groups of compounds in which the position trans to the benzenemalononitrile has been substituted by ketones and amides. Among the novel tyrphostins examined we found inhibitors which discriminate between the highly homologous EGF receptor kinase (HER1) and ErbB2/neu kinase (HER2). These findings may lead to selective tyrosine kinase blockers for the treatment of diseases in which ErbB2/neu is involved.

  DOI：

  10.1021/jm00110a022
• 作为产物：
  描述：

  N-甲基-P-氨基苯甲醚 在 三氯化铝 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 (N-methyl-5-methoxy-2-oxo-3-indolindine)malononitrile
  参考文献：
  名称：

  Tyrphostins. II. Heterocyclic and .alpha.-substituted benzylidenemalononitrile tyrphostins as potent inhibitors of EGF receptor and ErbB2/neu tyrosine kinases

  摘要：

  We have previously described a novel series of low molecular weight protein tyrosine kinase inhibitors which we named tyrphostins. The characteristic active pharmacophore of these compounds was the hydroxy-cis-benzylidenemalononitrile moiety. In this article we describe three novel groups of tyrphostins: (i) one group has the phenolic moiety of the cis-benzylidenemalononitrile replaced either with other substituted benzenes or with heteroaromatic rings, (ii) another is a series of conformationally constrained derivatives of hydroxy-cis-benzylidenemalononitriles in which the malononitrile moiety is fixed relative to the aromatic ring, and (iii) two groups of compounds in which the position trans to the benzenemalononitrile has been substituted by ketones and amides. Among the novel tyrphostins examined we found inhibitors which discriminate between the highly homologous EGF receptor kinase (HER1) and ErbB2/neu kinase (HER2). These findings may lead to selective tyrosine kinase blockers for the treatment of diseases in which ErbB2/neu is involved.

  DOI：

  10.1021/jm00110a022

文献信息

• Bi(OTf)₃-catalyzed C–H bond functionalization of azaarenes for the facile access to oxindoles featuring quaternary carbon centers
  作者：Beili Lu、Qilin Lu、Senyang Zhuang、Jiajia Cheng、Biao Huang

  DOI：10.1039/c4ra14144j

  日期：——

  Bi(OTf)₃-catalyzed sp³ C–H functionalization of 2-alkyl azaarenes to isatylidene malononitriles has been achieved to give oxindoles containing an all-carbon quaternary center.

  使用Bi(OTf)₃催化的2-烷基取代的氮杂环芳烃与亚硝基丙烷反应，实现了sp³ C–H官能团化，生成了含有全碳季碳中心的吲哚衍生物。

• Enantioselective Cascade Reaction of α-Cyano Ketones and Isatylidene Malononitriles: Asymmetric Construction of Spiro[4<i>H</i>-pyran-oxindoles]
  作者：Jin Xie、Wei-Long Xing、Feng Sha、Xin-Yan Wu

  DOI：10.1002/ejoc.201600432

  日期：2016.8

  α‐Cyano ketones have been used for the first time as Michael donors in the construction of chiral spiro compounds. In the presence of only 2 mol‐% of a chiral multifunctional organocatalyst, chiral spiro[4H‐pyran‐oxindole] derivatives were prepared in excellent yields with good‐to‐excellent enantioselectivities. This method provides a new approach to the synthesis of chiral spirocyclic oxindoles.

  α-氰基酮首次用作迈克尔供体用于构建手性螺环化合物。在仅2摩尔％的手性多功能有机催化剂的存在下，以优异的收率和良好至优异的对映选择性制备了手性螺[4 H-吡喃-氧吲哚]衍生物。该方法为合成手性螺环恶吲哚提供了一种新方法。
• Triphenylphosphine-Catalyzed [3+2] Cycloaddition of Allenoate and Active Olefins: Syntheses of Spirooxindole Derivatives
  作者：Xueshun Jia、Shanyan Guo、Rendong Wang、Jian Li、Chunju Li、Hongmei Deng

  DOI：10.1055/s-0030-1261188

  日期：2011.9

  A series of spiro compounds was achieved by triphenylphosphine-catalyzed [3+2] cycloaddition between active methylenemalononitrile and ethyl 2,3-butadienoate. Careful investigation showed that the present method had high regioselectivity. The products have a spirooxindole skeleton, which is a motif common in many natural products and pharmaceutically active compounds.

  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。
• Enantioselective construction of novel chiral spirooxindoles incorporating a thiazole nucleus
  作者：L.-Y. Cui、Y.-M. Wang、Z.-H. Zhou

  DOI：10.1039/c6ra14178a

  日期：——

  Asymmetric cascade Michael/cyclization reaction between 2-substituted thiazol-4-ones and 2-(2-oxoindolin-3-ylidene)malononitriles was investigated using a series of chiral bifunctional hydrogen-bonding organocatalysts. Good yields (up to 91%) and excellent enantioselectivities (up to 98% ee) were achieved by using a (1R,2R)-1,2-diphenylethane-1,2-diamine derived thiourea catalyst. This method provides an

  使用一系列手性双功能氢键有机催化剂研究了2-取代的噻唑-4-酮与2-（2-氧代吲哚-3-亚甲基）丙二腈之间的不对称级联迈克尔/环化反应。通过使用（1 R，2 R）-1,2-二苯乙烷-1,2-二胺衍生的硫脲催化剂，可以获得良好的收率（最高91％）和出色的对映选择性（最高98％ee）。该方法提供了一种优雅的合成途径，可用于获得具有潜在生物活性的新型噻唑融合螺硫醇。
• An Efficient Construction of CF ₃ ‐Substituted Spirooxindole‐Fused Benzo[a]quinolizidines by a Three‐Component Cyclization
  作者：Yijie Hu、Liufeiyang Ye、Jie Chen、Hui Zhang、Hongmei Deng、Jin‐Hong Lin、Weiguo Cao

  DOI：10.1002/ejoc.202100809

  日期：2021.8.13

  Since benzo[a]quinolizidine is a key subunit in numerous natural products and pharmaceuticals, its synthesis has received attention. Described herein is a convenient three-component cyclization for the efficient construction of CF 3 -substituted spirooxindole-fused benzo[a]quinolizidines by using CF3 -propiolate as a building block. This attractive protocol may find great synthetic utility as CF 3

  由于苯并[a]喹诺西啶是众多天然产物和药物中的关键亚基，其合成受到关注。本文描述了一种方便的三组分环化反应，用于通过使用 CF 3 -丙炔酸酯作为结构单元有效构建 CF 3 -取代的螺吲哚稠合的苯并[a]喹唑啉。由于在温和条件下通过一步环化安装了含 CF 3 的复杂结构，因此这种有吸引力的协议可能会具有很大的合成效用。