(±)-ethyl 1,6-dimethyl-2-oxo-4-(thiophen-2-yl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (±)-ethyl 1,6-dimethyl-2-oxo-4-(thiophen-2-yl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate
• 英文别名: Ethyl 1,6-dimethyl-2-oxo-4-(thiophen-2-yl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate；ethyl 3,4-dimethyl-2-oxo-6-thiophen-2-yl-1,6-dihydropyrimidine-5-carboxylate
• 化学式: C₁₃H₁₆N₂O₃S
• 分子量: 280.348
• InChiKey: DVQCDOLVZCZXFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 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：
  86.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ethyl 1,2,3,4-tetrahydro-1,6-dimethyl-2-oxopyrimidine-5-carboxylate 在 正丁基锂 、 硝酸 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 (±)-ethyl 1,6-dimethyl-2-oxo-4-(thiophen-2-yl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate
  参考文献：
  名称：

  A highly regio- and chemoselective addition of carbon nucleophiles to pyrimidinones. A new route to C4 elaborated Biginelli compounds

  摘要：

  Ethyl 6-methyl-pyrimidine-2-one-5-carboxylates react with C-nucleophiles in a diversity oriented synthetic sequence to afford C4 substituted congeners of medicinally potent Biginelli dihydropyrimidinones, in a highly regioselective manner. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2006.12.111

文献信息

• An Efficacious Protocol for 4-Substituted 3,4-Dihydropyrimidinones: Synthesis and Calcium Channel Binding Studies
  作者：Kamaljit Singh、Divya Arora、Danielle Falkowski、Qingxin Liu、Robert S. Moreland

  DOI：10.1002/ejoc.200900208

  日期：2009.7

  anion of enantiopure chiral auxiliary (1R,2S,5R)-(-)-methyl (S)-p-toluenesulfinate to afford C-4 substituted and enantiopure congeners of medicinally potent Biginelli dihydropyrimidinones. The calcium channel blocking activity of some of the compounds was evaluated and compared with nifedipine for their ability to relax a membrane depolarization induced contraction.

  1,2-二氢-1,6-二甲基/ 6-甲基-2-氧嘧啶-5-羧酸乙酯与C-亲核试剂以及对映纯手性助剂（1R，2S，5R）-（-）-甲基的阴离子反应（S）-对甲苯磺酸盐，可得到具有药效的比吉内利二氢嘧啶酮的C-4取代对映体和对映体纯同系物。对某些化合物的钙通道阻断活性进行了评估，并与硝苯地平比较了它们舒张膜去极化引起的收缩的能力。
• Solvent-Free Ball-Milling Biginelli Reaction by Subcomponent Synthesis
  作者：Prasit Kumar Sahoo、Anima Bose、Prasenjit Mal

  DOI：10.1002/ejoc.201501039

  日期：2015.11

  here an understanding of systems chemistry on small molecules through covalent mechanochemistry. As a proof-of-concept, the multicomponent Biginelli reaction by subcomponent synthesis was considered as a model system. Reactions were performed under solvent-free, metal-free, mechanochemical (ball milling) and ambient laboratory conditions. Br+-catalyzed oxidation of benzyl alcohols led to the product

  我们在这里报告通过共价机械化学对小分子的系统化学的理解。作为概念验证，通过子组分合成的多组分 Biginelli 反应被认为是一个模型系统。反应在无溶剂、无金属、机械化学（球磨）和环境实验室条件下进行。Br+催化苯甲醇氧化产生苯甲醛产物和副产物H+，它们分别作为组分和催化剂进一步促进，在同一反应釜内级联转化为二氢嘧啶酮。值得注意的是，在溶液中，反应体系在室温下即使在 24 小时后也无法重现。
• Discovery of 3,4-Dihydropyrimidin-2(1<i>H</i>)-ones As a Novel Class of Potent and Selective A_2B Adenosine Receptor Antagonists
  作者：Abel Crespo、Abdelaziz El Maatougui、Pierfrancesco Biagini、Jhonny Azuaje、Alberto Coelho、José Brea、María Isabel Loza、María Isabel Cadavid、Xerardo García-Mera、Hugo Gutiérrez-de-Terán、Eddy Sotelo

  DOI：10.1021/ml400185v

  日期：2013.11.14

  We describe the discovery and optimization of 3,4-dihydropyrimidin-2(1H)-ones as a novel family of (nonzanthine) A(2B) receptor antagonists that exhibit an unusually high selectivity profile. The Biginelli-based hit optimization process enabled a thoughtful exploration of the structure-activity and structure-selectivity relationships for this chemotype, enabling the identification of ligands that combine structural simplicity with excellent hA(2B) AdoR affinity and remarkable selectivity profiles.
• 3,4-Dihydropyrimidin-2(1<i>H</i>)-ones as Antagonists of the Human A_2B Adenosine Receptor: Optimization, Structure–Activity Relationship Studies, and Enantiospecific Recognition
  作者：María Majellaro、Willem Jespers、Abel Crespo、María J. Núñez、Silvia Novio、Jhonny Azuaje、Rubén Prieto-Díaz、Claudia Gioé、Belma Alispahic、José Brea、María I. Loza、Manuel Freire-Garabal、Carlota Garcia-Santiago、Carlos Rodríguez-García、Xerardo García-Mera、Olga Caamaño、Christian Fernandez-Masaguer、Javier F. Sardina、Angela Stefanachi、Abdelaziz El Maatougui、Ana Mallo-Abreu、Johan Åqvist、Hugo Gutiérrez-de-Terán、Eddy Sotelo

  DOI：10.1021/acs.jmedchem.0c01431

  日期：2021.1.14
• A highly regio- and chemoselective addition of carbon nucleophiles to pyrimidinones. A new route to C4 elaborated Biginelli compounds
  作者：Kamaljit Singh、Divya Arora、Sukhdeep Singh

  DOI：10.1016/j.tetlet.2006.12.111

  日期：2007.2

  Ethyl 6-methyl-pyrimidine-2-one-5-carboxylates react with C-nucleophiles in a diversity oriented synthetic sequence to afford C4 substituted congeners of medicinally potent Biginelli dihydropyrimidinones, in a highly regioselective manner. (c) 2006 Elsevier Ltd. All rights reserved.