3-乙酰基-2-氯-1-甲基吲哚 | 65287-75-4

• 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: 3-乙酰基-2-氯-1-甲基吲哚
• 英文名称: 3-acetyl-2-chloro-1-methylindole
• 英文别名: 1-(2-chloro-1-methylindol-3-yl)ethanone
• CAS: 65287-75-4
• 化学式: C₁₁H₁₀ClNO
• 分子量: 207.659
• InChiKey: LLZZEZGLIGDVLB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  22
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-乙酰基-2-氯-1-甲基吲哚 在 lithium methanethiolate 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 6.0h， 以66%的产率得到3-acetyl-1,3-dihydro-1-methyl-2H-indole-2-thione
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 4. Structure-Activity Relationships among N- and 3-Substituted 2,2'-Dithiobis(1H-indoles) for in vitro Inhibition of Receptor and Nonreceptor Protein Tyrosine Kinases

  摘要：

  A series of S-substituted 2,2'-dithiobis(1H-indoles) were synthesized 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, to extend the available structure-activity relationships for this series. The majority of the compounds were prepared either by reaction of 2-chloro-1-methylindole-3-carbonyl chloride with amines, followed by thiomethylation, demethylation, and oxidative dimerization, or by reaction of isocyanates with the anion of 1-methyl-2-indolinethione followed by dimerization. Overall, inhibitory activity is retained by analogues having a wide variety of side chains. A series of 3-carboxamide analogues had moderate to good activity against isolated EGFR (IC(50)s 1-20 mu M), with monoalkyl substitution of the carboxamide being optimal. Polar side chains were generally less effective than lipophilic ones, with benzyl being particularly effective. However, N,N-disubstitution was the most effective pattern for inhibition of pp60(v-src). A variety of substituted N-phenylcarboxamides had lower activity against EGFR than the parent derivative, and a N-thienylcarboxamide also had low activity. A series of 3-ketones, including methyl, phenyl, and furyl derivatives, showed moderate activity against the pp60(v-src) kinase, but were less effective against EGFR. The mechanism of inhibition of both kinases by these drugs was shown to be noncompetitive with respect to both ATP and peptide substrate. Selected compounds inhibited the growth of Swiss 3T3 cells with IC(50)s in the low micromolar range and inhibited bFGF-mediated intracellular tyrosine phosphorylation in the same cell line. Thiol inhibits the effects of the compounds, suggesting that one possible mechanism of inhibition is thiol-disulfide exchange with thiol-containing residues in the catalytic sites. Crystal structures of two representative compounds show a folded, V-shaped structure, with the disulfide bridge exposed, consistent with this hypothesis.

  DOI：

  10.1021/jm00001a011
• 作为产物：
  描述：

  2-吲哚酮 在 sodium hydride 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 5.25h， 生成 3-乙酰基-2-氯-1-甲基吲哚
  参考文献：
  名称：

  Ligand- and catalyst-free intramolecular C-S bond formation: direct access to indalothiochromen- 4-ones

  摘要：

  在无效配体和催化剂的条件下，开发了一种高效的分子内S-芳基化反应，直接从简单的二硫酯合成吲哚硫色素-4-酮。该方法尤其值得注意，因为它具有实验简单、广泛适用性和良好的官能团容忍性。

  DOI：

  10.1515/hc-2014-0206

文献信息

• Modulating Reactivity and Diverting Selectivity in Palladium-Catalyzed Heteroaromatic Direct Arylation Through the Use of a Chloride Activating/Blocking Group
  作者：Benoît Liégault、Ivan Petrov、Serge I. Gorelsky、Keith Fagnou

  DOI：10.1021/jo902515z

  日期：2010.2.19

  Through the introduction of an aryl chloride substituent, the selectivity of palladium-catalyzed direct arylation may be diverted to provide alternative regioisomeric products in high yields. In cases where low reactivity is typically observed, the presence of the carbon−chlorine bond can serve to enhance reactivity and provide superior outcomes. From a strategic perspective, the C−Cl bond is easily

  通过引入芳基氯取代基，可以改变钯催化的直接芳基化的选择性，从而以高收率提供替代的区域异构产物。在通常观察到低反应性的情况下，碳-氯键的存在可以起到增强反应性和提供优异结果的作用。从战略角度看，C-Cl键易于引入，可用于各种后续转化中，从而以最少的底物预活化提供大量高度官能化的杂环。还已经从力学上评估了C-Cl官能团对直接芳基化反应性的影响，并且观察到的反应性特征与协同的金属化-去质子化途径所预测的非常相关。
• Metal-free visible light-promoted synthesis of isothiazoles: a catalytic approach for N–S bond formation from iminyl radicals under batch and flow conditions
  作者：María Jesús Cabrera-Afonso、Sara Cembellín、Adnane Halima-Salem、Mateo Berton、Leyre Marzo、Abdellah Miloudi、M. Carmen Maestro、José Alemán

  DOI：10.1039/d0gc02618b

  日期：——

  applying photoredox catalysis. This simple strategy features mild conditions, broad scope and wide functional group tolerance representing a new enviromentally friendly option to prepare these highly valuable heterocycles. Furthermore, the synthetic value of the method is highlighted by the preparation of a natural product derivative and the implementation of the reaction in a continuous flow setup.

  已经开发了一种可持续的合成异噻唑的方法，该方法使用α-氨基氧酸助剂并应用光氧化还原催化。这种简单的策略具有温和的条件，广阔的范围和广泛的官能团耐受性，代表了制备这些极有价值的杂环的新的环境友好选择。此外，该方法的合成价值通过天然产物衍生物的制备和在连续流动装置中的反应的实施而突出。
• A Facile synthesis of Novel Indole-Based Chalcones (<i>E</i>)-1-(2-Chloro-1-Methyl-1<i>H</i>-Indol-3-Yl)-3-Arylprop-2-En-1-Ones
  作者：Wentao Gao、Shuai Lan、Yang Li、Hong Zhang、Mingqin Chang

  DOI：10.3184/174751914x14108592918139

  日期：2014.9

  A facile and general synthesis of 23 novel indole-based chalcones, ( E)-1-(2-chloro-1-methyl-1 H-indol-3-yl)-3-arylprop-2-en-1-ones, has been achieved in good yields of 71–89% by the Claisen–Schmidt condensation reaction of 3-acetyl-2-chloro- N-methylindole with variously substituted araldehydes using 1,4-dioxane as solvent in the presence of 5% aq. KOH. A similar reaction using furan-2- or thiophene-2-carbaldehyde gave analogous products in good yield, but an unexpected aldol reaction occurred with 2-nitrobenzaldehyde and the stable aldol product was isolated as the major product in a good yield of 73%.

  以 1,4- 二噁烷为溶剂，在 5%aq. KOH 的存在下，通过 3-乙酰基-2-氯-N-甲基吲哚与各种取代的醛的克莱森-施密特缩合反应，简单而普遍地合成了 23 种新型吲哚基查耳酮，即 ( E)-1-(2-chloro-1-methyl-1 H-indol-3-yl)-3-arylprop-2-en-1-ones ，产率高达 71-89%。使用呋喃-2-或噻吩-2-甲醛进行的类似反应得到了类似的产物，收率很高，但与 2-硝基苯甲醛发生了意想不到的醛醇反应，并分离出稳定的醛醇产物作为主要产物，收率高达 73%。
• Antagonists, their preparation and use
  申请人：Novo Nordisk A/S

  公开号：US05783575A1

  公开（公告）日：1998-07-21

  The present invention relates to therapeutically active non competitive antagonists, acting selectively at the metabotropic glutamate receptor. The novel compounds are useful in treating diseases in the central nervous system by modulating synaptic transmission via the metabotropic glutamate receptor.

  本发明涉及治疗活性的非竞争性拮抗剂，选择性地作用于代谢型谷氨酸受体。这些新型化合物可通过调节代谢型谷氨酸受体来治疗中枢神经系统疾病，从而调节突触传递。
• Thieno[2,3-b-indole derivatives and their use for treating central
  申请人：Novo Nordisk A/S

  公开号：US05536721A1

  公开（公告）日：1996-07-16

  The present invention relates to therapeutically active heterocyclic compounds, a method of preparing the same and to pharmaceutical compositions comprising the compounds. The novel compounds are useful in treating diseases in the central nervous system related to the metabotropic glutamate receptor system.

  本发明涉及治疗活性杂环化合物，其制备方法以及包含这些化合物的药物组合物。这些新型化合物在治疗与代谢型谷氨酸受体系统相关的中枢神经系统疾病方面具有用途。