methyl 3-(1-methyl-2-oxoindolin-3-yl)propanoate | 149287-24-1

• 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: methyl 3-(1-methyl-2-oxoindolin-3-yl)propanoate
• 英文别名: methyl 3-(1-methyl-2-oxo-3H-indol-3-yl)propanoate
• CAS: 149287-24-1
• 化学式: C₁₃H₁₅NO₃
• 分子量: 233.267
• InChiKey: UYGLBLLFWGZAHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 3-(1-methyl-2-oxoindolin-3-yl)propanoate 在 tetraphosphorus decasulfide 、 碳酸氢钠 作用下， 以 1,4-二氧六环 为溶剂， 以95%的产率得到methyl 3-(1-methyl-2-thioxo-3-indolinyl)propanoate
  参考文献：
  名称：

  Tyrosine kinase inhibitors. 1. Structure-activity relationships for inhibition of epidermal growth factor receptor tyrosine kinase activity by 2,3-dihydro-2-thioxo-1H-indole-3-alkanoic acids and 2,2'-dithiobis(1H-indole-3-alkanoic acids)

  摘要：

  A series of 2,3-dihydro-2-thioxo-1H-indole-3-alkanoic acids, and their methyl esters were prepared, the majority by oxidation of 1H-indole-3-alkanoic acids (DMSO/HCl), followed by thiation of the corresponding 2,3-dihydro-2-oxo-1H-indole-3-alkanoic acid esters. The monomeric thiones undergo facile and reversible oxidation to the corresponding 2,2'-dithiobis(1H-indole-3-alkanoic acids). The compounds were evaluated for their abilities to inhibit the tyrosine kinase activity of the epidermal growth factor receptor using a native complex contained in plasma membrane vesicles shed from cultured A431 cells, and to inhibit the growth of Swiss 3T3 mouse fibroblast in culture. Enzyme inhibitory activity is dependent on the length of the side chain, with propanoic acid derivatives showing the highest activity. The acids are generally significantly more potent than the corresponding esters, and the disulfides more active than the corresponding monomers. An ability to undergo the thione-thiol tautomerism necessary for dimerization is essential, with 3,3-disubstituted compounds being inactive. Overall, the data suggest that the disulfide is the more active form, with much of the activity of the monomeric thiones being due to varying degrees of conversion to the disulfide during the assay. In the growth inhibition assay, the methyl esters are more potent than their corresponding carboxylic acids, and the dimers are generally more potent than the monomers. The data show these compounds to be a novel and potent class of inhibitors of epidermal growth factor receptor tyrosine kinase activity.

  DOI：

  10.1021/jm00069a003
• 作为产物：
  描述：

  methyl 3-(3-hydroxy-1-methyl-2-oxoindolin-3-yl)propanoate 在 四氯化钛 、 锌 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 6.17h， 以62%的产率得到methyl 3-(1-methyl-2-oxoindolin-3-yl)propanoate
  参考文献：
  名称：

  低价钛对靛红与α,β-不饱和羰基化合物的还原偶联

  摘要：

  靛红与 α,β-不饱和羰基化合物在 0 °C 下通过 Zn-TiCl 4在 THF 中的还原偶联得到一对一的偶联产物，3-羟基-3-烷氧基吲哚。由α,β-不饱和酯获得的偶联产物通过在催化剂中回流转化为相应的螺-γ-内酯。PPTS/苯。2:1 偶联产物 3,3-双（2-碳甲氧基乙基）羟吲哚是通过 Zn-TiCl 4在 THF 中在 30 °C 下用丙烯酸甲酯还原靛红形成的。靛红与丙烯酸甲酯还原偶联得到的一对一偶联产物通过Zn-TiCl 4还原为3-(2-甲氧基乙基)羟吲哚在 30 °C 的 THF 中。将 3-(2- 碳甲氧基乙基) 羟吲哚加入丙烯腈中得到 3-(2- 碳甲氧基乙基)-3-(2-氰乙基) 羟吲哚。

  DOI：

  10.1246/bcsj.20210357

文献信息

• Diastereo‐ and Enantioselective Construction of Vicinal All‐Carbon Quaternary Stereocenters via Iridium/Europium Bimetallic Catalysis
  作者：Wei Wang、Fangqing Zhang、Yangbin Liu、Xiaoming Feng

  DOI：10.1002/anie.202208837

  日期：2022.9.26

  dual-metal-catalyzed asymmetric allylic alkylation reaction has been developed by makig use of challenging trisubstituted allylic esters and nucleophilic C3-substituted oxindole derivatives. A variety of allylated products bearing vicinal all-carbon quaternary stereocenters could be obtained in good yields with high to excellent diastereoselectivities (up to 20 : 1 dr) and enantioselectivities (up to 99 % ee)

  通过使用具有挑战性的三取代烯丙基酯和亲核 C3-取代的羟吲哚衍生物，开发了一种前所未有的 Ir/Eu 双金属催化的不对称烯丙基烷基化反应。可以以良好的收率获得具有高至优异的非对映选择性（高达 20 : 1 dr）和对映选择性（高达 99 % ee）的各种带有连位全碳四元立体中心的烯丙基化产物。
• US5464861A
  申请人：——

  公开号：US5464861A

  公开（公告）日：1995-11-07
• US5556874A
  申请人：——

  公开号：US5556874A

  公开（公告）日：1996-09-17
• Tyrosine kinase inhibitors. 1. Structure-activity relationships for inhibition of epidermal growth factor receptor tyrosine kinase activity by 2,3-dihydro-2-thioxo-1H-indole-3-alkanoic acids and 2,2'-dithiobis(1H-indole-3-alkanoic acids)
  作者：Andrew M. Thompson、Gordon W. Rewcastle、Moana Tercel、Ellen M. Dobrusin、David W. Fry、Alan J. Kraker、William A. Denny

  DOI：10.1021/jm00069a003

  日期：1993.8

  A series of 2,3-dihydro-2-thioxo-1H-indole-3-alkanoic acids, and their methyl esters were prepared, the majority by oxidation of 1H-indole-3-alkanoic acids (DMSO/HCl), followed by thiation of the corresponding 2,3-dihydro-2-oxo-1H-indole-3-alkanoic acid esters. The monomeric thiones undergo facile and reversible oxidation to the corresponding 2,2'-dithiobis(1H-indole-3-alkanoic acids). The compounds were evaluated for their abilities to inhibit the tyrosine kinase activity of the epidermal growth factor receptor using a native complex contained in plasma membrane vesicles shed from cultured A431 cells, and to inhibit the growth of Swiss 3T3 mouse fibroblast in culture. Enzyme inhibitory activity is dependent on the length of the side chain, with propanoic acid derivatives showing the highest activity. The acids are generally significantly more potent than the corresponding esters, and the disulfides more active than the corresponding monomers. An ability to undergo the thione-thiol tautomerism necessary for dimerization is essential, with 3,3-disubstituted compounds being inactive. Overall, the data suggest that the disulfide is the more active form, with much of the activity of the monomeric thiones being due to varying degrees of conversion to the disulfide during the assay. In the growth inhibition assay, the methyl esters are more potent than their corresponding carboxylic acids, and the dimers are generally more potent than the monomers. The data show these compounds to be a novel and potent class of inhibitors of epidermal growth factor receptor tyrosine kinase activity.
• Reductive Coupling of Isatins with α,β-Unsaturated Carbonyl Compounds by Low-Valent Titanium
  作者：Naoki Kise、Yuki Mitsui、Toshihiko Sakurai

  DOI：10.1246/bcsj.20210357

  日期：2022.1.15

  The reductive coupling of isatins with α,β-unsaturated carbonyl compounds by Zn-TiCl4 in THF at 0 °C gave one-to-one coupled products, 3-hydoxy-3-alkyloxindoles. The coupled products obtained from α,β-unsaturated esters were transformed to the corresponding spiro-γ-lactones by refluxing in cat. PPTS/benzene. The two-to-one coupled products, 3,3-bis(2-carbomethoxyethyl)oxindoles, were formed by the

  靛红与 α,β-不饱和羰基化合物在 0 °C 下通过 Zn-TiCl 4在 THF 中的还原偶联得到一对一的偶联产物，3-羟基-3-烷氧基吲哚。由α,β-不饱和酯获得的偶联产物通过在催化剂中回流转化为相应的螺-γ-内酯。PPTS/苯。2:1 偶联产物 3,3-双（2-碳甲氧基乙基）羟吲哚是通过 Zn-TiCl 4在 THF 中在 30 °C 下用丙烯酸甲酯还原靛红形成的。靛红与丙烯酸甲酯还原偶联得到的一对一偶联产物通过Zn-TiCl 4还原为3-(2-甲氧基乙基)羟吲哚在 30 °C 的 THF 中。将 3-(2- 碳甲氧基乙基) 羟吲哚加入丙烯腈中得到 3-(2- 碳甲氧基乙基)-3-(2-氰乙基) 羟吲哚。