1-methyl-5-cyan-1,3-dihydroindol-2-one | 156136-72-0

• 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: 1-methyl-5-cyan-1,3-dihydroindol-2-one
• 英文别名: 5-cyano-N-methyl-2-indolone；5-cyano-1-methyloxindole；1-Methyl-2-oxoindoline-5-carbonitrile；1-methyl-2-oxo-3H-indole-5-carbonitrile
• CAS: 156136-72-0
• 化学式: C₁₀H₈N₂O
• 分子量: 172.186
• InChiKey: RWAACBAKMUEXIZ-UHFFFAOYSA-N

物化性质

• 沸点：
  444.9±45.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-methyl-5-cyan-1,3-dihydroindol-2-one 在 tetraphosphorus decasulfide 、 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 以41%的产率得到5-cyano-1-methyl-2-indolinethione
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 3. Structure-Activity Relationships for Inhibition of Protein Tyrosine Kinases by Nuclear-Substituted Derivatives of 2,2'-Dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamide)

  摘要：

  A series of indole-substituted 2,2'-dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamides) were prepared and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and the nonreceptor pp60(v-src) tyrosine kinase. The compounds were synthesized by conversion of appropriate 1-methyloxindoles to 1-methyl-2-indolinethiones with P2S5 followed by subsequent reaction with NaH and phenyl isocyanate and oxidative dimerization of the resulting 2,3-dihydro-N-phenyl-2-thioxo-1H-indole-3-carboxamides. The parent compound and many of the substituted analogues were moderately potent inhibitors of both kinase enzymes, but no clear relationships were seen between substitution on the indole ring and inhibitory activity, While 4-substituted compounds were generally inactive, 5-substituted derivatives with electron-withdrawing groups showed inhibitory activity. However, none of the substituted compounds showed significantly better activity than the unsubstituted parent compound. There was generally a good correlation between activity against the EGFR and pp60(v-src) kinases, but several compounds did show some specificity (>20-fold) of inhibition; 5-Cl and 5-Br derivatives preferentially inhibited pp60(v-src), while the 5-CF3 compound preferentially inhibited EGFR. Selected compounds from the series were found to inhibit the growth of Swiss 3T3 fibroblasts with IC(50)s in the range 2-25 mu M, the most active being 4-substituted derivatives. The compounds inhibited bFGF-mediated protein tyrosine phosphorylation in intact cells more effectively than EGFR- or PDGF-mediated phosphorylation.

  DOI：

  10.1021/jm00039a016
• 作为产物：
  描述：

  4-氨基-3-溴苯腈 在 5 mol% Pd/C 、 sodium hydride 、 caesium carbonate 、 三乙胺 、 三环己基膦 、 三甲基乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 3.34h， 生成 1-methyl-5-cyan-1,3-dihydroindol-2-one
  参考文献：
  名称：

  多相钯催化分子内 C(sp3)H α-芳基化用于绿色合成羟吲哚

  摘要：

  在此，我们展示了我们开发一种废物最小化方案的结果，该方案使用环戊基甲基醚 (CPME) 作为安全和绿色的反应介质，钯碳 (Pd/C) 作为可重复使用的催化剂来合成羟吲哚。该协议有效地应用于各种基材，提供具有出色产量、最小金属污染和最小废物产生的产品。催化剂被回收并重复使用连续四次，没有任何明显的效率损失。此外，产品通过简单的庚烷沉淀分离，无需色谱分离，CPME和庚烷均被回收。为所提出的协议计算的低 E 因子反映了废物最小化。

  DOI：

  10.1016/j.mcat.2022.112211

文献信息

• Synthesis of 2-Oxindoles from Substituted Indoles by Hypervalent-Iodine Oxidation
  作者：Xinpeng Jiang、Cong Zheng、Lijun Lei、Kai Lin、Chuanming Yu

  DOI：10.1002/ejoc.201701807

  日期：2018.3.29

  The practical and efficient conversion of indoles into the corresponding 2‐oxindoles is achieved under neutral conditions using a hypervalent iodine reagent. This oxidation is amenable to different substituted indoles.

  在中性条件下，使用高价碘试剂可实现将吲哚实际有效地转化为相应的2-吲哚。该氧化适合于不同的取代的吲哚。
• 一种取代吲哚在中性条件下直接合成取代2- 吲哚酮的方法
  申请人：浙江工业大学

  公开号：CN108129377B

  公开（公告）日：2020-01-07

  本发明涉及一种取代吲哚在中性条件下直接合成取代2‑吲哚酮的方法。该方法如下：室温下依次加入比例为1:1~1:20的有机溶剂和水，然后加入高碘试剂，升温至40~160℃后加入吲哚，反应1~8小时后得到取代2‑吲哚酮类化合物。本发明的主要创新点在于在中性条件下通过吲哚直接氧化合成取代2‑吲哚酮，革除了强酸性试剂的使用，具有原料廉价易得、操作简便、底物普适性好和反应收率较高等优点。
• Rewcastle Gordon W., Palmer Brian D., Dobrusin Ellen M., Fry David W., Kr+, J. Med. Chem, 37 (1994) N 13, S 2033-2042
  作者：Rewcastle Gordon W., Palmer Brian D., Dobrusin Ellen M., Fry David W., Kr+

  DOI：——

  日期：——
• 2-THIOINDOLES (SELENOINDOLES) AND RELATED DISULFIDES (SELENIDES) WHICH INHIBIT PROTEIN TYROSINE KINASES AND WHICH HAVE ANTITUMOR PROPERTIES
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0654024A1

  公开（公告）日：1995-05-24
• US5464861A
  申请人：——

  公开号：US5464861A

  公开（公告）日：1995-11-07