7-氯-1-甲基-1,3-二氢-吲哚-2-硫酮 | 100831-27-4

• 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
• 中文名称: 7-氯-1-甲基-1,3-二氢-吲哚-2-硫酮
• 英文名称: 7-Chloro-1-methyl-1,3-dihydro-indole-2-thione
• 英文别名: 7-chloro-1-methyl-3H-indole-2-thione
• CAS: 100831-27-4
• 化学式: C₉H₈ClNS
• 分子量: 197.688
• InChiKey: HDKDRGUTJAOMST-UHFFFAOYSA-N

物化性质

• 沸点：
  287.0±50.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  35.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  7-氯-1-甲基-1,3-二氢-吲哚-2-硫酮 在 air 、 sodium hydride 作用下， 以 甲醇 为溶剂， 生成 7-chloro-2-[[7-chloro-3-(C-hydroxy-N-phenylcarbonimidoyl)-1-methylindol-2-yl]disulfanyl]-1-methyl-N-phenylindole-3-carboximidic acid
  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：

  7-chloro-1-methylindolin-2-one 在 tetraphosphorus decasulfide 、 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 以90%的产率得到7-氯-1-甲基-1,3-二氢-吲哚-2-硫酮
  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

文献信息

• Enantioselective synthesis of indolo[2,3-b]-dihydrothiopyranones via [3+3] cycloaddition of chiral α,β-unsaturated acylammonium salts
  作者：Jing-Hai Jin、Xiang-Yu Li、Xiaoyan Luo、Wei-Ping Deng

  DOI：10.1016/j.tet.2018.09.024

  日期：2018.11

  nucleophile-catalyzed Michael addition/proton transfer/lactonization (NCMPL) organocascade process of chiral α,β-unsaturated acylammonium salts and indoline-2-thiones is described, which delivers the indolo[2,3-b]dihydrothiopyranone motifs in high yields (up to 97%) with good to excellent enantioselectivities (up to 98% ee).

  描述了亲核催化剂催化的手性α，β-不饱和酰基铵盐和二氢吲哚-2-硫酮的迈克尔加成/质子转移/内酯化（NCMPL）有机级联反应，该反应可高产率地产生吲哚[2,3- b ]二氢噻喃酮基序（高达97％）具有良好至优异的对映选择性（高达98％ee）。
• 一种手性吲哚并噻喃化合物的合成方法
  申请人：苏州大学

  公开号：CN104497007B

  公开（公告）日：2017-01-18

  本发明公开了一种手性吲哚并噻喃类化合物的合成方法，具体为以硫代吲哚酮与苯甲醛丙二腈为反应物，在手性多功能1R,2R‑二苯基乙二胺硫脲催化剂催化下，在溶剂中合成得到产物。本发明公开的方法原料简单易得，反应条件温和，后处理简单方便，适用的底物范围广，收率高，对映选择性高；由此合成得到的产物可用以合成药物和杀虫剂的中间体。
• Asymmetric Construction of Spiro[thiopyranoindole-benzoisothiazole] Scaffold via a Formal [3 + 3] Spiroannulation
  作者：Xiang Chen、Jun-Qi Zhang、Shao-Jie Yin、Hai-Yan Li、Wei-Qun Zhou、Xing-Wang Wang

  DOI：10.1021/acs.orglett.5b01951

  日期：2015.9.4

  An enantioselective formal thio[3 + 3] spiroannulation reaction of indoline-2-thiones to 1-azadienes has been developed by the use of a quinine-derived bifunctional tertiary amine-thiourea catalyst, which furnished a series of optically active spiro[thiopyranoindole-benzoisothiazole] heterocycles with a spiro quaternary C–N/C–S stereogenic centers in high yields with good to excellent diastereo- and

  通过使用奎宁衍生的双官能叔胺-硫脲催化剂开发了吲哚啉-2-硫酮与1-氮杂二烯的对映体选择性硫[3 + 3]螺环化反应，该催化剂提供了一系列旋光性螺[thiopyranoindole-具有螺环季铵化C–N / C–S立体异构中心的苯并异噻唑]杂环化合物，其高收率具有出色的非对映选择性和对映选择性。
• Access to Tetrahydrothiopyrano[2,3‐b]Indole Derivatives via Zinc‐Catalyzed Asymmetric [3+3] Annulation of Indoline‐2‐Thiones with Yne–Enones
  作者：Dan‐Dan Cui、Jian‐Wen Shi、Tong Wang、Yuan‐Zhao Hua、Min‐Can Wang、Guang‐Jian Mei、Jun‐Long Niu、Shi‐Kun Jia

  DOI：10.1002/adsc.202400072

  日期：2024.4.23

  We report herein an enantioselective [3 + 3] annulation of indoline‐2‐thiones with yne−enones by chiral dinuclear zinc catalysts via a Brønsted base and Lewis acid cooperative activation. This transformation proceeded through sequential conjugate addition, allenyl ketone formation and intramolecular sulfa‐Michael 6‐endo‐trig cyclization. A range of enantioenriched tetrahydrothiopyrano[2,3‐b]indole

  我们在此报告了通过手性双核锌催化剂通过布朗斯台德碱和路易斯酸协同活化，二氢吲哚-2-硫酮与炔烯酮的对映选择性[3 + 3]环化。这种转化通过顺序共轭加成、丙二烯基酮形成和分子内磺胺-Michael 6-endo-trig环化进行。以中等产率获得了一系列带有环外双键的对映体富集四氢吡喃并[2,3-b]吲哚衍生物，具有优异的立体选择性（高达 20:1 dr、20:1 Z/E 比和 95% ee）。还探索了后期功能化、大规模实验和进一步衍生化。
• Enantioselective Construction of Functionalized Thiopyrano-Indole Annulated Heterocycles via a Formal Thio [3 + 3]-Cyclization
  作者：Xiang Chen、Zheng-Hang Qi、Shao-Yun Zhang、Ling-Pei Kong、Yong Wang、Xing-Wang Wang

  DOI：10.1021/ol503210q

  日期：2015.1.2

  A formal thio [3 + 3]-cyclization catalyzed by a DPEN-derived chiral thiourea has been reported for the construction of optically active thiopyrano-indole annulated heterocyclic compounds in high yields with excellent enantioselectivities. The high reactivity between indoline-2-thione (keto-S) and 2-benzylidenemalononitrile has also been supported by density functional theory (DFT) calculations.