methyl 4-(2-hydroxyphenyl)-6-methyl-2-oxo-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: methyl 4-(2-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
• 英文别名: methyl 4-(2-hydroxyphenyl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxylate
• 化学式: C₁₃H₁₄N₂O₄
• 分子量: 262.265
• InChiKey: SRTXUWOWNMZWAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(2-氯乙氧基)甲基]膦酸二乙酯 、 methyl 4-(2-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Design, synthesis, in silico, and in vitro evaluation of novel pyrimidine phosphonates with cytotoxicity against breast cancer cells

  摘要：

  Pyrimidine derivatives are widely used for the treatment of breast cancer and rapid efforts are contributing to develop highly potential novel molecules. In view of this, in this study, novel pyrimidine phosphonate molecules were designed so as to inhibit aromatase, a potential target of breast cancer. Quantitative structure activity relationship descriptors were defined and they revealed that the molecules have an effective and safer drug-like properties, which also supported by absorption, distribution, metabolism, and excretion study. Molecular docking of these compounds into the aromatase active site revealed that they are showing strong interaction forming H-bonds and arene cationic interactions. The ligand-receptor complex of compound 6i showed a best docking score of -15.776 kcal/mol among all. Hence, this compound was synthesized and tested in vitro at different concentrations of 25, 50, 100, and 200 mu g/mL against MDA-MB-231 adenocarcinoma breast cancer cells and it exhibited excellent antiproliferative activity and also induced apoptosis. The results from in silico structure activity relationships, molecular docking study and in vitro assays suggesting the compound as a potential source of chemotherapeutic drug for the treatment and management of breast cancer.

  DOI：

  10.1007/s00044-013-0628-y
• 作为产物：
  描述：

  13-methoxycarbonyl-9-methyl-11-oxo-8-oxa-10,12-diazatricyclo[7.3.1.0^2,7]trideca-2,4,6-triene 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 生成 methyl 4-(2-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
  参考文献：
  名称：

  水杨醛与2-羟基-1-萘醛的Biginelli反应研究

  摘要：

  水杨醛和2-羟基-1-萘醛与乙酰乙酸乙酯或甲基乙酸酯，苯甲酰乙酸乙酯和尿素的Biginelli反应已在反应产物的结构和反应条件中进行了重新研究。水杨醛与乙酰乙酸乙酯和乙酰乙酸甲酯可生成氧桥连的三环四氢嘧啶，而苯甲酰乙酸乙酯则可提供唯一的正常3,4-二氢嘧啶-2-酮。2-羟基-1-萘乙醛与乙酰乙酸甲酯和乙酰乙酸甲酯形成三环化合物。立体效应可能是决定产物二分法形成的主要决定因素。关于Biginelli产品结构的先前有争议的结果已经讨论并解决。

  DOI：

  10.1002/jhet.1785

文献信息

• Synthesis, crystal structure and antibacterial studies of dihydropyrimidines and their regioselectively oxidized products
  作者：Alakbar E. Huseynzada、Christian Jelch、Haji Vahid N. Akhundzada、Sarra Soudani、Cherif Ben Nasr、Aygun Israyilova、Filippo Doria、Ulviyya A. Hasanova、Rana F. Khankishiyeva、Mauro Freccero

  DOI：10.1039/d0ra10255e

  日期：——

  Known methods of synthesis of dihydropyrimidines and their oxidized products were modified, the impact of hydrogen bonds on stabilization of preferred tautomer and biological activities were studied.

  对已知的二氢嘧啶及其氧化产物的合成方法进行了改进，研究了氢键对优选互变异构体稳定和生物活性的影响。
• [bmim(SO 3 H)][OTf]/[bmim][X] and Zn(NTf 2 ) 2 /[bmim][X] (X = PF 6 and BF 4 ); efficient catalytic systems for the synthesis of tetrahydropyrimidin-ones (-thiones) via the Biginelli reaction
  作者：Hemantkumar M. Savanur、Rajesh G. Kalkhambkar、Gopalakrishnan Aridoss、Kenneth K. Laali

  DOI：10.1016/j.tetlet.2016.05.103

  日期：2016.7

  facile, high yielding, and simple method for the synthesis of a library of dihydropyrimidinones (and -thiones) via the one-pot Biginelli reaction of aldehydes is reported. The method employs the Brønsted acidic IL [bmim(SO3H][OTf] or Zn(NTf2)2 as catalyst along with the readily available imidazolium-ILs as solvent, and exhibits good potential for the recycling and reuse of the IL solvent.

  报道了一种通过醛的一锅Biginelli反应合成二氢嘧啶酮（和-硫酮）文库的简便，高产率和简单的方法。该方法采用布朗斯台德酸性IL [bmim（SO 3 H] [OTf]或Zn（NTf 2）2作为催化剂，并使用易获得的咪唑类ILs作为溶剂，并具有回收和再利用IL溶剂的良好潜力。 。
• Air‐stable zirconium (IV)‐salophen perfluorooctanesulfonate as a highly efficient and reusable catalyst for the synthesis of 3,4‐dihydropyrimidin‐2‐(1H)‐ones/thiones under solvent‐free conditions
  作者：Ningbo Li、Yijun Wang、Feijun Liu、Xin Zhao、Xinhua Xu、Quan An、Keming Yun

  DOI：10.1002/aoc.5454

  日期：2020.3

  An air‐stable complex of zirconium (IV)‐salophen perfluorooctanesulfonate (1) was successfully synthesized by reacting Zr (salphen)Cl2 and C8F17SO3Ag. Complex 1 was characterized and studied by different techniques (NMR, IR, HRMS, TG‐DSC, conductivity and acidity measurements), and was found to be air‐stable, water tolerant, thermally stable and strongly Lewis‐acidic. Complex 1 exhibited high catalytic

  通过使Zr（salphen）Cl 2与C 8 F 17 SO 3 Ag反应成功合成了一种空气稳定的锆（IV）-salophen全氟辛烷磺酸盐（1）。配合物1通过不同的技术（NMR，IR，HRMS，TG-DSC，电导率和酸度测量）进行了表征和研究，被发现具有空气稳定性，耐水性，热稳定性和强路易斯酸性。络合物1在无溶剂条件下通过醛，1,3-二羰基化合物和脲/硫脲的Biginelli反应合成3,4-二氢嘧啶-2-（1H）-酮/硫酮具有很高的催化效率。此外，复数1可以重复使用5次，而催化效率的变化却很小。与以前报道的方法相比，该方案的重要特征是无溶剂条件，反应时间短，底物相容性广，效率高和可重复使用性好。
• Soluble polymer-supported synthesis of Biginelli compounds
  作者：Min Xia、Yan-Guang Wang

  DOI：10.1016/s0040-4039(02)01850-6

  日期：2002.10

  An efficient and general liquid-phase synthesis of Biginelli compounds has been developed. Polyethylene glycol (PEG) bound acetoacetate reacted with urea and aldehydes under reflux or solvent-free microwave irradiation conditions to afford PEG-supported 3,4-dihydropyrimidin-2(1H)-ones. The desired 3,4-dihydropyrimidin-2(1H)-ones were cleaved from the polymer support under mild conditions in high yields

  已经开发了一种高效且通用的Biginelli化合物液相合成方法。在回流或无溶剂微波辐射条件下，聚乙二醇（PEG）结合的乙酰乙酸酯与脲和醛反应，得到PEG负载的3,4-二氢嘧啶-2（1 H）-one。在温和的条件下以高收率和高纯度从聚合物载体上裂解出所需的3，4-二氢嘧啶-2（1 H）-1 。
• One-Pot Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones Catalyzed by Acidic Ionic Liquids Under Solvent-Free Conditions
  作者：Jianzhou Gui、Dan Liu、Chan Wang、Feng Lu、Jingzhao Lian、Heng Jiang、Zhaolin Sun

  DOI：10.1080/00397910902774042

  日期：2009.9.8

  Abstract The acidic ionic liquids were new catalysts for the one-pot Biginelli reaction coupling of aldehyde, 1,3-dicarbonyl compound, and urea to afford the corresponding dihydropyrimidinones in good yields under solvent-free conditions. The catalysts could be recycled and reused five times without a noticeable decrease in catalytic activity.

  摘要 酸性离子液体是一种新型催化剂，可用于醛、1,3-二羰基化合物和尿素的一锅Biginelli反应偶联，在无溶剂条件下以良好的收率得到相应的二氢嘧啶酮。催化剂可以循环使用五次，催化活性没有明显下降。