(Z)-2-tert-butyl-3-(2-morpholino-2-oxoethylidene)isoindolin-1-one | 1415251-83-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: (Z)-2-tert-butyl-3-(2-morpholino-2-oxoethylidene)isoindolin-1-one
• 英文别名: (E)-2-tert-butyl-3-(2-morpholino-2-oxoethylidene)isoindolin-1-one；(3E)-2-tert-butyl-3-(2-morpholin-4-yl-2-oxoethylidene)isoindol-1-one
• CAS: 1415251-83-0
• 化学式: C₁₈H₂₂N₂O₃
• 分子量: 314.384
• InChiKey: KXWJNTMXRNDNGJ-NTCAYCPXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (Z)-2-tert-butyl-3-(2-morpholino-2-oxoethylidene)isoindolin-1-one 、 N-benzylmethylene nitrone 以 甲苯 为溶剂， 反应 4.0h， 以10%的产率得到(1RS,4'SR)-2'-benzyl-2-tert-butyl-4'-(morpholine-4-carbonyl)spiro[isoindoline-1,5'-isoxazolidin]-3-one
  参考文献：
  名称：

  Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

  摘要：

  一系列的螺[异吲哚-1,5-异恶唑啉]-3(2H)-酮已经通过1,3-偶极环加成反应合成，反应中使用N-苄基亚硝基甲烷与异吲哚-3-亚甲基-1-酮。该过程的区域和立体选择性已经通过计算方法理性化。所得化合物在9-22 μM范围内表现出细胞毒性和抗增殖活性。生物测试表明抗肿瘤活性可能与蛋白质-蛋白质p53-MDM2相互作用的抑制有关。对接测量支持生物数据。

  DOI：

  10.3762/bjoc.12.278
• 作为产物：
  描述：

  N-tert-butyl-2-ethynylbenzamide 在 一氧化碳 、 氧气 、 potassium iodide 、 palladium(II) iodide 作用下， 以 乙腈 为溶剂， 100.0 ℃ 、4.05 MPa 条件下， 生成 (Z)-2-tert-butyl-3-(2-morpholino-2-oxoethylidene)isoindolin-1-one
  参考文献：
  名称：

  A new approach to isoindolinone derivatives by sequential palladium iodide-catalyzed oxidative aminocarbonylation–heterocyclization of 2-ethynylbenzamides

  摘要：

  A novel approach to functionalized isoindolinone derivatives 3 is presented. It is based on a cascade process, consisting of PdI2/KI-catalyzed oxidative monoaminocarbonylation of secondary 2-ethynylbenzamides 1 with nucleophilic secondary amines 2, followed by intramolecular conjugate addition of the arylamido group to the alkynylamido group of the intermediate alkynylamides. Products have been obtained in high to excellent yields starting from different N-alkyl 2-ethynylbenzamides and amines, under relatively mild conditions (100 degrees C under 40 atm of a 4:1 mixture of CO-air), working in a MeCN-amine mixture (2:1, v/v) for 5-15 h. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.09.109

文献信息

• Divergent Palladium Iodide Catalyzed Multicomponent Carbonylative Approaches to Functionalized Isoindolinone and Isobenzofuranimine Derivatives
  作者：Raffaella Mancuso、Ida Ziccarelli、Donatella Armentano、Nadia Marino、Salvatore V. Giofrè、Bartolo Gabriele

  DOI：10.1021/jo500281h

  日期：2014.4.18

  formation of 3-[(dialkylcarbamoyl)methylene]isoindolin-1-ones through the intermediate formation of the corresponding 2-ynamide derivatives followed by intramolecular nucleophilic attack by the nitrogen of the benzamide moiety on the conjugated triple bond. On the other hand, 3-[(alkoxycarbonyl)methylene]isobenzofuran-1(3H)imines were selectively obtained when the oxidative carbonylation of 2-alkynylbenzamides

  当使2-炔基苯甲酰胺在PdI 2催化的氧化羰基化条件下反应时，经历不同的反应途径，这取决于外部亲核试剂的性质和反应条件。因此，在作为外部亲核试剂的仲胺存在下，带有末端三键的2-乙炔基苯甲酰胺的氧化羰基化选择性地导致通过中间体形成3-[（（二烷基氨基甲酰基）亚甲基]异吲哚啉-1-酮形成相应的2-炔酰胺衍生物，然后通过共轭三键上的苯甲酰胺基团的氮分子进行分子内亲核攻击。另一方面，3-[（烷氧羰基）亚甲基]异苯并呋喃-1（3 H当在醇R'OH（例如甲醇或乙醇）作为外部亲核试剂和HC（OR）存在下，进行带有末端或内部三键的2-炔基苯甲酰胺的氧化羰基化反应时，有选择地获得亚胺′）3作为脱水剂，必须避免底物水解。在该后者的情况下，导致isobenzofuranimine反应路径对应于5-外型-挖分子内配位上与金属中心随后烷氧基羰基的三键的苯甲酰胺部分的氧的亲核攻击。代表性产品的结构已通过X射线晶体学分析确认。
• A new approach to isoindolinone derivatives by sequential palladium iodide-catalyzed oxidative aminocarbonylation–heterocyclization of 2-ethynylbenzamides
  作者：Bartolo Gabriele、Raffaella Mancuso、Ida Ziccarelli、Giuseppe Salerno

  DOI：10.1016/j.tetlet.2012.09.109

  日期：2012.12

  A novel approach to functionalized isoindolinone derivatives 3 is presented. It is based on a cascade process, consisting of PdI2/KI-catalyzed oxidative monoaminocarbonylation of secondary 2-ethynylbenzamides 1 with nucleophilic secondary amines 2, followed by intramolecular conjugate addition of the arylamido group to the alkynylamido group of the intermediate alkynylamides. Products have been obtained in high to excellent yields starting from different N-alkyl 2-ethynylbenzamides and amines, under relatively mild conditions (100 degrees C under 40 atm of a 4:1 mixture of CO-air), working in a MeCN-amine mixture (2:1, v/v) for 5-15 h. (C) 2012 Elsevier Ltd. All rights reserved.
• Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2<i>H</i>)-ones as potential inhibitors of the MDM2-p53 interaction
  作者：Salvatore V Giofrè、Santa Cirmi、Raffaella Mancuso、Francesco Nicolò、Giuseppe Lanza、Laura Legnani、Agata Campisi、Maria A Chiacchio、Michele Navarra、Bartolo Gabriele、Roberto Romeo

  DOI：10.3762/bjoc.12.278

  日期：——

  A series of spiro[isoindole-1,5-isoxazolidin]-3(2H)-ones has been synthesized by 1,3-dipolar cycloaddition of N-benzylnitrone with isoindolin-3-methylene-1-ones. The regio- and stereoselectivity of the process have been rationalized by computational methods. The obtained compounds show cytotoxic properties and antiproliferative activity in the range of 9–22 μM. Biological tests suggest that the antitumor activity could be linked to the inhibition of the protein–protein p53-MDM2 interaction. Docking measurements support the biological data.

  一系列的螺[异吲哚-1,5-异恶唑啉]-3(2H)-酮已经通过1,3-偶极环加成反应合成，反应中使用N-苄基亚硝基甲烷与异吲哚-3-亚甲基-1-酮。该过程的区域和立体选择性已经通过计算方法理性化。所得化合物在9-22 μM范围内表现出细胞毒性和抗增殖活性。生物测试表明抗肿瘤活性可能与蛋白质-蛋白质p53-MDM2相互作用的抑制有关。对接测量支持生物数据。