methyl 1-benzyl-2-oxopyrrolidine-3-carboxylate | 71725-74-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: methyl 1-benzyl-2-oxopyrrolidine-3-carboxylate
• 英文别名: 1-benzyl-2-oxo-pyrrolidine-3-carboxylic acid methyl ester
• CAS: 71725-74-1
• 化学式: C₁₃H₁₅NO₃
• 分子量: 233.267
• InChiKey: SWNNNDKMQKYQBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 1-benzyl-2-oxopyrrolidine-3-carboxylate 在 甲酸 、 potassium tert-butylate 、 palladium diacetate 、 1,2-双(二苯基膦)乙烷 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 24.5h， 生成 1-benzyl-3-(difluoromethyl)pyrrolidin-2-one
  参考文献：
  名称：

  A Unified Strategy for the Synthesis of Difluoromethyl- and Vinylfluoride-Containing Scaffolds

  摘要：

  Here, we report a general method for the synthesis of quaternary and tertiary difluoromethylated compounds and their vinylfluoride analogues. The strategy, which relies on a two-step sequence featuring a C-selective electrophilic difluoromethylation and either a palladium-catalyzed decarboxylative protonation or a Krapcho decarboxylation, is practical, scalable, and high yielding. Considering the generality of the method and the attractive properties offered by the difluoromethyl group, this approach provides a valuable tool for late-stage functionalization and drug development.

  DOI：

  10.1021/acs.orglett.9b02887
• 作为产物：
  描述：

  1-苄基-2-吡咯烷酮 、 氯甲酸甲酯 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以76%的产率得到methyl 1-benzyl-2-oxopyrrolidine-3-carboxylate
  参考文献：
  名称：

  A Unified Strategy for the Synthesis of Difluoromethyl- and Vinylfluoride-Containing Scaffolds

  摘要：

  Here, we report a general method for the synthesis of quaternary and tertiary difluoromethylated compounds and their vinylfluoride analogues. The strategy, which relies on a two-step sequence featuring a C-selective electrophilic difluoromethylation and either a palladium-catalyzed decarboxylative protonation or a Krapcho decarboxylation, is practical, scalable, and high yielding. Considering the generality of the method and the attractive properties offered by the difluoromethyl group, this approach provides a valuable tool for late-stage functionalization and drug development.

  DOI：

  10.1021/acs.orglett.9b02887

文献信息

• Targeting Alzheimer's disease by investigating previously unexplored chemical space surrounding the cholinesterase inhibitor donepezil
  作者：Divan G. van Greunen、Werner Cordier、Margo Nell、Chris van der Westhuyzen、Vanessa Steenkamp、Jenny-Lee Panayides、Darren L. Riley

  DOI：10.1016/j.ejmech.2016.10.036

  日期：2017.2

  A series of twenty seven acetylcholinesterase inhibitors, as potential agents for the treatment of Alzheimer's disease, were designed and synthesised based upon previously unexplored chemical space surrounding the molecular skeleton of the drug donepezil, which is currently used for the management of mild to severe Alzheimer's disease. Two series of analogues were prepared, the first looking at the

  根据之前围绕药物多奈哌齐分子骨架未开发的化学空间，设计和合成了一系列二十七个乙酰胆碱酯酶抑制剂，这些药物可作为治疗阿尔茨海默氏病的潜在药物，目前已用于治疗轻度至重度阿尔茨海默氏病。制备了两个系列的类似物，第一个看待用不同尺寸的饱和含氮环系统取代多奈哌齐中的哌啶环，第二个看待多奈哌齐中茚满酮和哌啶环之间引入不同的连接基。活性最高的类似物5,6-二甲氧基-1-氧代-2,3-二氢-1H-茚满-2-基-1-苄基哌啶-4-羧酸酯（67）的体外IC50值为0.03±0。抗乙酰胆碱酯酶为07μM，未观察到细胞毒性（IC50> 100μM，SH-SY5Y细胞系）。相比之下，多奈哌齐的IC50为0.05±0.06μM，观察到的细胞毒性IC50为15.54±1.12μM。分子建模显示活性和乙酰胆碱酯酶活性位点的计算机内结合之间有很强的相关性。
• Enecarbamates as Imine Surrogates:  Nucleophilic Addition of 1,3-Dicarbonyl Compounds to Enecarbamates
  作者：Shū Kobayashi、Tomas Gustafsson、Yusuke Shimizu、Hiroshi Kiyohara、Ryosuke Matsubara

  DOI：10.1021/ol0620186

  日期：2006.10.1

  [reaction: see text] Novel Mannich-type reactions of 1,3-dicarbonyl compounds with enecarbamates have been developed. Stable and storable enecarbamates work as surrogates of aliphatic aldehyde-derived imines, which are known to be difficult to isolate and store.

  [反应：见正文]已经开发了1，3-二羰基化合物与烯氨基甲酸酯的新型曼尼希型反应。稳定的和可储存的碳酸氨基甲酸酯可作为脂肪族醛衍生的亚胺的替代物，已知这些亚胺难以分离和储存。
• Stereoselective Spirolactam Synthesis via Palladium Catalyzed Arylative Allene Carbocyclization Cascades
  作者：Meiling Li、Darren J. Dixon

  DOI：10.1021/ol101425y

  日期：2010.9.3

  A diastereoselective arylative carbocyclization of pro-nucleophile-linked allenes with aryl and heteroaryl halides to provide spirocyclic lactam products with moderate to high diastereoselectivities and good yields under Pd(0) catalysis is reported. Being operationally simple and tolerant of multiple points of diversity, this complexity building reaction cascade, in which two new carbon-carbon bonds and one new heterocyclic ring are created, should be of high value in both complex natural product synthesis as well as compound library synthesis.
• Substituted aryl malonamates as new serine β-lactamase substrates: Structure–activity studies
  作者：S.A. Adediran、D. Cabaret、J.-F. Lohier、M. Wakselman、R.F. Pratt

  DOI：10.1016/j.bmc.2009.10.056

  日期：2010.1

  A series of substituted aryl malonamates have been prepared. These compounds are analogues of aryl phenaceturates where the amido side chain has been replaced by a retro-amide. Like the phenaceturates, these compounds are substrates of typical class A and class C beta-lactamases, particularly of the latter, and of soluble DD-peptidases. The effect of substituents alpha to the ester carbonyl group on turnover by these enzymes is similar to that in the phenaceturates. On the other hand, N-alkylation of the side chain amide of malonamates, but not of phenaceturates, retains the susceptibility of the compounds to hydrolysis by beta-lactamases. This reactivity is not enhanced, however, by bridging the amide nitrogen and C alpha atoms. A phosphonate analogue of the malonamates was found to be an irreversible inhibitor of the beta-lactamases. These results, therefore, provide further evidence for the covalent access of compounds bearing retroamide side chains to the active sites of beta-lactam-recognizing enzymes. (C) 2009 Elsevier Ltd. All rights reserved.
• SANTANIELLO E.; VAGHI D.; MANZOCCHI A., SYNTH. COMMUN., 1979, 9, NO 7, 619-624
  作者：SANTANIELLO E.、 VAGHI D.、 MANZOCCHI A.

  DOI：——

  日期：——