2-(1-甲基吲哚-3-基)-2-氧代-乙酸乙酯 | 25055-54-3

• 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: 2-(1-甲基吲哚-3-基)-2-氧代-乙酸乙酯
• 英文名称: ethyl 2-(1-methyl-1H-indol-3-yl)-2-oxoacetate
• 英文别名: ethyl 1H-1-methylindol-3-ylglyoxylate；ethyl (1-methylindolyl-3)-glyoxylate；ethyl N-methyl indole-3-glyoxylate；(1-methyl-indol-3-yl)-oxo-acetic acid ethyl ester；1-Methyl-indol-3-ethylglyoxylat；Ethyl-1-methylindol-3-glyoxylat；Ethyl (1-methyl-1H-indol-3-yl)(oxo)acetate；ethyl 2-(1-methylindol-3-yl)-2-oxoacetate
• CAS: 25055-54-3
• 化学式: C₁₃H₁₃NO₃
• 分子量: 231.251
• InChiKey: DFLGCVGOABTHCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  48.3
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2918300090

反应信息

• 作为反应物：
  描述：

  2-(1-甲基吲哚-3-基)-2-氧代-乙酸乙酯 在 正丁基锂 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 为溶剂， 反应 3.25h， 生成 3-(1-methyl-1H-indol-3-yl)-1,6-dioxaspiro[4.5]dec-3-en-2-one
  参考文献：
  名称：

  铋（III）催化炔丙基二醇酯的双环化：合成[5,5]-和[6,5]-氧杂螺内酯的统一方法

  摘要：

  在此，我们公开了一种前所未有的分子内级联策略，用于构建 α,β-不饱和 [5,5]- 和 [6,5]-氧杂螺内酯，该策略利用 π-亲电子路易斯酸催化的 5 -exo-dig或 6-炔丙基二醇酯环化的exo-dig模式，然后是脱水和螺内酯化步骤。此外，半保护底物还可以在最佳反应条件下以相同的容易程度和可观的收率递送各自的氧杂螺内酯。

  DOI：

  10.1039/d1ob00974e
• 作为产物：
  描述：

  ethyl 2-(1-methyl-1H-indol-3-yl)-2-(p-tolylamino)acetate 在 2,2,6,6-四甲基哌啶氧化物 、 水 、 lithium perchlorate 作用下， 以 乙腈 为溶剂， 反应 12.0h， 生成 2-(1-甲基吲哚-3-基)-2-氧代-乙酸乙酯
  参考文献：
  名称：

  吲哚与醛的电化学促成C3-甲酰化和酰化作用

  摘要：

  本文报道的是吲哚与各种醛的氧化交叉偶联的有效策略。该策略基于两步转化，通过众所周知的曼尼希型反应和羰基引入的C–N键裂解实现。关键步骤是曼尼希产品的C–N键断裂—是通过电化学实现的。这种策略（包含40多个示例）可确保出色的官能团耐受性以及药物分子的后期功能化。

  DOI：

  10.1021/acs.orglett.9b02433

文献信息

• A new one step synthesis of maleimides by condensation of glyoxylate esters with acetamides
  作者：Margaret M. Faul、Leonard L. Winneroski、Christine A. Krumrich

  DOI：10.1016/s0040-4039(98)02594-5

  日期：1999.2

  Bisphenyl, Bisheteroaryl, indolylaryl and indolylcycloalkyl maleimides are prepared in one step and 67–99% yield by condensation of glyoxylate esters with acetamides using a 1.0 M solution of potassium tert-butoxide in THF. The mechanism of the reaction is discussed.

  使用1.0 M叔丁醇钾的THF溶液，通过乙醛酸酯与乙酰胺的缩合，可一步制备联苯，二异芳基，吲哚基芳基和吲哚基环烷基马来酰亚胺，收率67-99％。讨论了反应机理。
• Design, Synthesis, and Biological Evaluation of 3,4-Diarylmaleimides as Angiogenesis Inhibitors
  作者：Christian Peifer、Thomas Stoiber、Eberhard Unger、Frank Totzke、Christoph Schächtele、Dieter Marmé、Ruth Brenk、Gerhard Klebe、Dieter Schollmeyer、Gerd Dannhardt

  DOI：10.1021/jm0580297

  日期：2006.2.1

  The new analogue 2 of combretastatin A-4 was discovered to be an inhibitor of tubulin polymerization with an IC50 of 7.6 microM and reduced angiogenesis in the in vivo chick embryo model. Interestingly, in a series of 2,3-diarylmaleimides closely related to this lead, no other compound was found to be active in the tubulin polymerization assay. However, by screening in the in vivo chick embryo assay

  发现康美他汀A-4的新类似物2是微管蛋白聚合的抑制剂，在体内鸡胚模型中的IC50为7.6 microM，并减少了血管生成。有趣的是，在一系列与该铅紧密相关的2，3-二芳基马来酰亚胺中，在微管蛋白聚合测定中未发现其他化合物具有活性。然而，通过在体内进行筛选，将雏鸡胚胎测定法10鉴定为有效的血管生成抑制剂，表明了另一种靶标。确实，分子建模研究表明在模型激酶CDK2的ATP结合位点有一个合理的10结合模式。根据这些结果，在10种类似的12种蛋白激酶中筛选了10种类似物的抑制活性，发现10种对VEGF-R2的高亲和力表明IC50为2.5 nM。
• Copper(II)-Catalyzed Benzylic C(sp³)–H Aerobic Oxidation of (Hetero)Aryl Acetimidates: Synthesis of Aryl-α-ketoesters
  作者：Yogesh Kumar、Yogesh Jaiswal、Amit Kumar

  DOI：10.1021/acs.joc.6b02176

  日期：2016.12.16

  straightforward method is developed in this paper for the synthesis of α-ketoesters through copper-catalyzed aerobic oxidation of (hetero)aryl acetimidates using molecular oxygen as a sustainable oxidant. The reaction represents the first example of the direct synthesis of aryl-α-ketoesters from arylacetimidates through the aerobic oxidation of a benzylic C(sp3)–H (C═O) bond in moderate to good yield. This transformation

  本文开发了一种简单的方法，使用分子氧作为可持续的氧化剂，通过铜催化的（杂）芳基乙酰亚氨酸的需氧氧化，合成α-酮酸酯。该反应代表了通过对苄基C （sp3） -H（C═O）键进行有氧氧化以中等至良好收率，由芳基乙酰亚氨酸酯直接合成芳基-α-酮酸酯的第一个例子。这种转化在温和的反应条件下与多种底物一起发生，并利用了容易获得的氧化剂和催化剂。这种转化的合成效用通过放大合成得到了证明。还提出了合理的反应机理。
• Easy Access to Phenanthridinones via Metal-Free Cascade Benzannulation and C–N Bond Formation
  作者：Preeti、Kailas V. Kallurkar、Prathama S. Mainkar、Raju Adepu、Srivari Chandrasekhar

  DOI：10.1021/acs.orglett.3c03040

  日期：2023.12.1

  A concise route for the synthesis of dihydrobenzo[j]phenanthridinones has been disclosed through an aryne annulation strategy under metal-free reaction conditions. The reaction involves multiple C–C and C–N bond cleavages/formations via Diels–Alder reaction, aromatization-driven C–N bond cleavage, and amide formation.

  通过在无金属反应条件下的芳基环化策略，公开了一种合成二氢苯并[ j ]菲啶酮的简明路线。该反应涉及通过狄尔斯-阿尔德反应、芳构化驱动的 C-N 键断裂和酰胺形成进行的多个 C-C 和 C-N 键断裂/形成。
• Structure-Based Design Leads to the Identification of Lithium Mimetics That Block Mania-like Effects in Rodents. Possible New GSK-3β Therapies for Bipolar Disorders
  作者：Alan P. Kozikowski、Irina N. Gaisina、Hongbin Yuan、Pavel A. Petukhov、Sylvie Y. Blond、Allison Fedolak、Barbara Caldarone、Paul McGonigle

  DOI：10.1021/ja068969w

  日期：2007.7.1

  More than two million American adults, or approximately one percent of the population 18 years or older, suffer from bipolar disorder. Current treatments include the so-called "mood stabilizers," lithium and valproic acid. Both are relatively dated drugs that are only partially effective and produce various undesirable side effects including weight gain. Based upon continued efforts to understand the molecular target for lithium, it now appears that specific inhibitors of the enzyme glycogen synthase kinase-3 beta (GSK-3 beta) may mimic the therapeutic action of mood stabilizers and might therefore allow for the design of improved drugs for treating patients with bipolar disorder as well as certain neurodegenerative disorders. Furthermore, the pro-apoptotic properties of the GSK-3 enzyme suggest the possible use of such inhibitors as neuroprotective agents. In fact, neuroprotection may contribute to the treatment of mood disorders. The present chemistry, modeling, and biology efforts have identified 3-benzofuranyl-4-indolylmaleimides as potent and relatively selective GSK-3 beta inhibitors. The best ligand in this series (having a K-i value of 4.6 nM against GSK-3 beta) was studied in a novel mouse model of mania that has recently been validated with several clinically effective mood stabilizers. This study presents the first demonstration of the efficacy of a GSK-3 beta inhibitor in this mouse model of mania. Selective brain penetrable GSK-3 ligands like those described herein become valuable research tools in better defining the role of this multifaceted kinase in both physiological and pathophysiological events.