1-methyl-5-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one | 156136-54-8

• 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-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one
• 英文别名: 5-trifluoromethyl-1-methyloxindole；1-methyl-5-(trifluoromethyl)oxindole；1-Methyl-5-(trifluoromethyl)indolin-2-one；1-methyl-5-(trifluoromethyl)-3H-indol-2-one
• CAS: 156136-54-8
• 化学式: C₁₀H₈F₃NO
• 分子量: 215.175
• InChiKey: SRKDPYINSFEZSC-UHFFFAOYSA-N

物化性质

• 沸点：
  339.6±42.0 °C(Predicted)
• 密度：
  1.348±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-methyl-5-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one 在 tetraphosphorus decasulfide 、 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 以96%的产率得到2H-吲哚-2-硫酮,1,3-二氢-1-甲基-5-(三氟甲基)-
  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-溴三氟甲苯 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-(trifluoromethyl)-1,3-dihydro-2H-indol-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

• Chemoselective S_N2′ Allylations of Detrifluoroacetylatively In Situ Generated 3-Fluoroindolin-2-one-Derived Tertiary Enolates with Morita–Baylis–Hillman Carbonates
  作者：Yi Zhu、Haibo Mei、Jianlin Han、Vadim A. Soloshonok、Jie Zhou、Yi Pan

  DOI：10.1021/acs.joc.7b02409

  日期：2017.12.15

  n derivatives has been described. The SN2′ substitution takes place in a highly chemoselective manner as no corresponding SN2 products were observed in the reaction mixtures. Due to the excellent stereochemical outcome, the reactions seem to have an apparent synthetic value for the preparation of structurally new fluorinated oxindoles.

  已经描述了在未催化的与森田-贝利斯-希尔曼衍生物的未催化反应中，原位生成的三氟乙酰化叔三氟乙酰基的S N 2'反应类型的第一个例子。在S Ñ 2'取代在一个高度化学选择性地无相应的S Ñ 2产物在反应混合物中观察到的。由于出色的立体化学结果，该反应对于制备结构上新的氟化羟吲哚似乎具有明显的合成价值。
• Regioselective electrophilic trifluoromethylation of indolines, oxindoles and indoles in superacid
  作者：Sébastien Debarge、Kenza Kassou、Hélène Carreyre、Bruno Violeau、Marie-Paule Jouannetaud、Jean-Claude Jacquesy

  DOI：10.1016/j.tetlet.2003.10.192

  日期：2004.1

  Treatment of indolines and N-acylindoles with HF/SbF5/CCl4 yields 6-trifluoro derivatives (indole numbering) whereas indoles and oxindoles give the 5-trifluoro derivatives in good yield. (C) 2003 Published by Elsevier Ltd.
• 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
• US4160032A
  申请人：——

  公开号：US4160032A

  公开（公告）日：1979-07-03