5-Chloro-1-methyl-1,3-dihydro-indole-2-thione | 110994-27-9

• 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: 5-Chloro-1-methyl-1,3-dihydro-indole-2-thione
• 英文别名: 5-chloro-1-methyl-3H-indole-2-thione
• CAS: 110994-27-9
• 化学式: C₉H₈ClNS
• 分子量: 197.688
• InChiKey: FWHMIGLPVFQMJI-UHFFFAOYSA-N

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：

  5-Chloro-1-methyl-1,3-dihydro-indole-2-thione 在 air 、 sodium hydride 作用下， 以 甲醇 为溶剂， 生成 dithiobis(1H-indole-3-carboxamide) deriv. 10g
  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：

  5-chloro-1-methylindolin-2-one 在 tetraphosphorus decasulfide 、 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 生成 5-Chloro-1-methyl-1,3-dihydro-indole-2-thione
  参考文献：
  名称：

  AlCl3介导的二氢吲哚-2-硫酮与酰基环丙烷、双环丙烷和螺环环丙烷的开环反应

  摘要：

  研究了AlCl 3介导的二氢吲哚-2-硫酮与各种酰基环丙烷、双环丙烷和螺环环丙烷的亲核开环反应。合成了一系列用吲哚硫基官能化的酮，产率从中等到良好。此外，将4-吲哚硫基丁-1-酮化学转化为二氢-2H-噻吩并[2,3- b ]吲哚和砜，以进一步扩大合成实用性和结构复杂性。

  DOI：

  10.1039/d3ob00909b

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）。
• Access to Substituted Dihydrothiopyrano[2,3-<i>b</i>]indoles via Sequential Rearrangements During <i>S</i>-Alkylation and Au-Catalyzed Hydroarylation on Indoline-2-thiones
  作者：Mukund Jha、Ganesh M. Shelke、T. Stanley Cameron、Anil Kumar

  DOI：10.1021/jo5025943

  日期：2015.5.15

  the synthesis of indole-fused dihydrothiopyrans has been developed from indoline-2-thiones. The protocol involves the synthesis of conjugated ene-yne-substituted indole-sulfides, a gold(III)-catalyzed rearrangement of the ene-yne side chain followed by intramolecular hydroarylation via C3–H functionalization of the indole core. This new synthesis of functionalized tricyclic indole derivatives through

  从二氢吲哚-2-硫酮开发了一种有效的合成吲哚稠合的二氢硫吡喃的方法。该协议涉及共轭烯-炔取代的吲哚硫化物的合成，金（III）催化的烯-炔侧链的重排，然后通过吲哚核的C3-H官能化进行分子内氢化。通过顺序重排的功能化三环吲哚衍生物的这种新合成本质上是相当普遍的
• Stereocontrolled Construction of the 3,4-Dihydrothiacarbazol-2(9<i>H</i>)-one Skeleton by Using Bifunctional Squaramide-Catalyzed Cascade Reactions
  作者：Shanren Chen、Jianping Pan、Youming Wang、Zhenghong Zhou

  DOI：10.1002/ejoc.201403078

  日期：2014.12

  approach for the stereocontrolled construction of the 3,4-dihydrothiacarbazol-2(9H)-one skeleton has been developed. In the presence of a bifunctional squaramide catalyst that was derived from L-tert-leucine, the asymmetric tandem Michael/thiolysis reactions of 9-methylindoline-2-thiones and N-alkynoylphthalimides proceeded efficiently to furnish the desired 3,4-dihydrothiacarbazol-2(9H)-one derivatives

  3,4-dihydrothiacarbazol-2(9H)-one 骨架立体控制结构的有效方法已经开发出来。在衍生自 L-叔亮氨酸的双功能方酸酰胺催化剂存在下，9-甲基二氢吲哚-2-硫酮和 N-炔基邻苯二甲酰亚胺的不对称串联迈克尔/硫解反应有效地提供了所需的 3,4-二氢噻咔唑-2 (9H)-一种衍生物，收率令人满意，对映选择性高（高达 98% ee）。
• Synthesis of indole-annulated sulfur heterocycles using copper-catalysed C–N coupling and palladium-catalysed direct arylation
  作者：Ganesh M. Shelke、Mukund Jha、Anil Kumar

  DOI：10.1039/c6ob00117c

  日期：——

  A simple and efficient method for the synthesis of biologically relevant 5H-benzo[4,5][1,3]thiazino[3,2-a]indoles and 5,7-dihydroisothiochromeno[3,4-b]indoles has been developed via intramolecular copper catalysed Ullmann-type C–N coupling and palladium catalysed direct arylation from the corresponding precursors 2-(2-bromobenzylthio)-1H-indole and 2-(2-bromobenzylthio)-1-methyl-1H-indole, respectively

  一种简单有效的合成生物学上相关的5 H-苯并[4,5] [1,3]噻嗪基[3,2- a ]吲哚和5,7-二氢异硫代色素[3,4- b ]吲哚的方法开发通过分子内铜催化的Ullmann型C-N偶联和钯从相应的前体2-（2- bromobenzylthio）-1催化芳基化直接ħ -吲哚和2-（2- bromobenzylthio）-1-甲基-1- ħ -吲哚，分别具有良好至优异的产量。
• Access to thiopyrano[2,3-b]indole via tertiary amine-catalyzed formal (3+3) annulations of β′-acetoxy allenoates with indoline-2-thiones
  作者：Chunjie Ni、Yuwen Zhang、Yading Hou、Xiaofeng Tong

  DOI：10.1039/c6cc09788j

  日期：——

  The DABCO-catalyzed formal (3+3) annulations of [small beta]'-acetoxy allenoates with indoline-2-thiones are described, which provide a facile access to thiopyrano[2,3-b]indole under mild reaction conditions. The reaction might proceed SN2'-SN2' type process...

  描述了DABCO催化的吲哚啉-2-硫酮的小β'-乙酰氧基脲酸酯的正式（3 + 3）环化反应，可在温和的反应条件下轻松获得噻喃并[2,3-b]吲哚。反应可能会继续进行SN2'-SN2'类型的过程...