ethyl 4-(anthracen-9-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: ethyl 4-(anthracen-9-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
• 英文别名: ethyl 4-(9-anthryl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate；ethyl 4-(9-anthryl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate；ethyl 4-(9-anthryl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one-5-carboxylate；Ethyl 4-(anthracen-9-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydro pyrimidine-5-carboxylate；ethyl 4-anthracen-9-yl-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxylate
• 化学式: C₂₂H₂₀N₂O₃
• 分子量: 360.412
• InChiKey: LFXWUOHCVXGABP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 4-(anthracen-9-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 在 potassium peroxomonosulphate 、 cobalt(II) nitrate 作用下， 以 水 、 乙腈 为溶剂， 以35%的产率得到ethyl 4-(9-anthryl)-pyrimidin-2(1H)-one-5-carboxylate
  参考文献：
  名称：

  An unusual oxidation–dealkylation of 3,4-dihydropyrimidin-2(1H)-ones mediated by Co(NO3)2·6H2O/K2S2O8 in aqueous acetonitrile

  摘要：

  4-Aryl-6-methyl-3,4-dihydropyrimidin-2(1H)-one (DHPM) scaffolds of Biginelli type were oxidized using Co(II)/S2O82- and the reaction afforded 6-unsubstituted pyrimidin-2(1H)-ones through an unprecedented dealkylation process. 4-Alkyl DHPMs under similar conditions afforded yet another unusual product, ethyl tetrahydropyrimidin-2,4(1H,3H)-dione-5-carboxylate. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.11.010
• 作为产物：
  描述：

  乙酰乙酸乙酯 、 尿素 、 9-蒽甲醛 在 4-(3-silylpropyl)morpholine, sulfate acidic ionic liquid functionalized magnetite-silica core-shell nanoparticles 作用下， 以 乙醇 为溶剂， 反应 1.17h， 以89%的产率得到ethyl 4-(anthracen-9-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
  参考文献：
  名称：

  一种锚定在磁铁矿纳米颗粒上的布朗斯台德酸性离子液体作为 Biginelli 反应的新型可回收非均相催化剂

  摘要：

  本研究采用简单有效的方法制备固定磁铁矿纳米粒子的离子液体。Fe 3 O 4纳米粒子通过化学共沉淀法制备。然后，通过Stober方法在磁芯上涂覆SiO 2壳。最后，将 CPTES（氯丙基三乙氧基硅烷）和吗啉涂覆在 SiO 2上贝壳。硫酸吗啉，一种酸性离子液体，成功地与磁铁矿纳米粒子 (Mag@Morph-AIL) 结合，用作制备 3,4-二氢嘧啶酮的有效催化剂。与以前的工作相比，使用外部磁体轻松分离纳米催化剂，催化剂的可回收性、无毒、多功能性和高稳定性，再加上反应时间短和产率高，使本方案对合成非常有用的标题产品。通过 1 H-NMR、13 C-NMR、FT-IR、扫描电子显微镜、X-射线衍射和元素分析对合成的产物和催化剂进行了确认。

  DOI：

  10.1039/d0ra09929e

文献信息

• An Amine Functionalized Metal–Organic Framework as an Effective Catalyst for Conversion of CO₂ and Biginelli Reactions
  作者：Ashish Verma、Dinesh De、Kapil Tomar、Parimal K. Bharadwaj

  DOI：10.1021/acs.inorgchem.7b01286

  日期：2017.8.21

  could be easily removed along with the guest molecules in the lattice upon activation to afford the desolvated framework 1′. This produced exposed metal sites that, along with the pendant amine groups incorporated in the ligand, generated a coordination space in the framework to make it an outstanding heterogeneous catalyst for the chemical fixation of CO2 with various epoxides under atmospheric pressure

  高度多孔的和热稳定的阴离子的Zn（II）-framework，[（CH 3）2 NH 2 + ] 2 [的Zn 3（（μ 3 -O））（L）2（H 2 O）]·4DMF·已经采用溶剂热技术合成了具有暴露的金属位点和胺侧基的2H 2 O} n（1）。该阴离子3D骨架显示出2％的互穿度，空隙体积为45.1％。它具有一个3,6-c二叉网络，并带有稀有的3,6-conn拓扑。活化后，金属结合的水配体可以很容易地与晶格中的客体分子一起去除，从而提供去溶剂化的骨架1′。这产生了暴露的金属位点，这些位点与配体中引入的侧基胺基团一起在骨架中产生了配位空间，使其成为出色的非均相催化剂，用于在大气压力下以及在三种条件下用各种环氧化物对CO 2进行化学固定。组分Biginelli与不同的醛，乙酰乙酸乙酯和尿素反应生成二氢嘧啶酮。
• NbCl₅-catalyzed Rapid and Efficient Synthesis of 3,4-Dihydropyrimidinones Under Ambient Conditions
  作者：J. S. Yadav、B. V. S. Reddy、Jaishri J. Naidu、K. Sadashiv

  DOI：10.1246/cl.2004.926

  日期：2004.7

  Three-component condensation of an aldehyde, 1,3-dicarbonyl compound and urea or thiourea proceeds smoothly at room temperature in the presence of 5 mol % of NbCl5 under extremely mild conditions to afford the corresponding 3,4-dihydropyrimidines in high to quantitative yields. This method is very useful for the synthesis of a wide range of dipyrimidinones at room temperature from aromatic, heterocyclic, and aliphatic aldehydes.

  在极温和的条件下，5摩尔％NbCl5的存在下，醛、1,3-二羰基化合物和脲或硫脲的三组分缩合在室温下顺利进行，获得相应的3,4-二氢嘧啶，在高至定量的产率下。这种方法非常适用于从芳香、杂环和脂肪醛室温合成广泛范围的双嘧啶酮。
• Xanthine Oxidase Inhibitory and Molecular Docking Studies on Pyrimidones
  作者：Humaira Zafar、Sarosh Iqbal、Sumaira Javaid、Khalid M. Khan、Muhammad I. Choudhary

  DOI：10.2174/1573406413666171129224919

  日期：2018.7.6

  Background: Xanthine oxidase is an important enzyme which catalyzes the production of uric acid and superoxide anion from xanthine. The over-production of these products leads to different disease conditions. For instance, uric acid is responsible for hyperuricemia, gout, and arthritis, while superoxide anion contributes to the oxidative stress, and related diseases. Hence XO is an important pharmacological target for the treatment of a range of diseases. Methods: Based on the structural resemblance of pyrimidines with xanthine, a series of previously synthesized ethyl 6- methyl-2-oxo-1, 2, 3, 4-tetrahydro-5-pyrimidinecarboxylate derivatives were evaluated for XO inhibitory activity. Results: Among 25 pyrimidone derivatives, 22 were found to be good to weak inhibitors with IC50 values in the range of 14.4 - 418 µM. Compounds 3, 14, 15, 18, and 21-23 were significant inhibitors, and thus analyzed for their kinetic parameters. Among them compounds 14, 15, 18, and 23 were competitive, 21 and 22 showed non-competitive, while 23 was a mixed-type of inhibitor. Molecular docking studies highlighted the interactions of these inhibitors with critical amino acids of XO, such as Val1011, Phe649, Lys771, and others. Moreover, the cytotoxicity studies on these selected inhibitors showed all these compounds to be non-cytotoxic. Conclusion: These non-cytotoxic, significant XO inhibitors can thus be further investigated for the treatment of hyperuricemia, and gout.

  背景：黄嘌呤氧化酶是催化黄嘌呤产生尿酸和超氧阴离子的一种重要酶。这些产物的过度产生会导致不同的疾病。例如，尿酸是高尿酸血症、痛风和关节炎的罪魁祸首，而超氧阴离子则会导致氧化应激和相关疾病。因此，XO 是治疗一系列疾病的重要药理靶点。 方法：根据嘧啶与黄嘌呤结构相似的特点，对之前合成的一系列 6-甲基-2-氧代-1，2，3，4-四氢-5-嘧啶羧酸乙酯衍生物的 XO 抑制活性进行了评估。 结果：在 25 种嘧啶酮衍生物中，有 22 种是良好至较弱的抑制剂，其 IC50 值在 14.4 - 418 µM 之间。化合物 3、14、15、18 和 21-23 具有显著的抑制作用，因此对其动力学参数进行了分析。分子对接研究强调了这些抑制剂与 XO 的关键氨基酸（如 Val1011、Phe649、Lys771 等）之间的相互作用。结论：因此，可以进一步研究这些无细胞毒性的 XO 重要抑制剂，以治疗高尿酸血症和痛风。
• LiClO4-Catalyzed One-Pot Synthesis of Dihydropyrimidinones: An Improved Protocol for Biginelli Reaction
  作者：Jhillu S. Yadav、Basi V. Subba Reddy、R. Srinivas、C. Venugopal、T. Ramalingam

  DOI：10.1055/s-2001-15229

  日期：——

  perchlorate efficiently catalyzes the three-component condensation reaction of aldehyde, β-keto ester and urea in refluxing acetonitrile to afford the corresponding dihydropyrimidinones in high yields under neutral conditions. LiOTf is also found to be an efficient catalyst for the synthesis of dihydropyrimidinones from aldehyde, β-keto ester and urea.

  高氯酸锂在中性条件下高效催化醛、β-酮酯和脲在回流乙腈中的三组分缩合反应，以高收率得到相应的二氢嘧啶酮。LiOTf 还被发现是从醛、β-酮酯和尿素合成二氢嘧啶酮的有效催化剂。
• Synthesis of novel 3,4-dihydropyrimidinones on water soluble solid support catalyzed by indium triflate
  作者：P. Shanmugam、G. Annie、P. T. Perumal

  DOI：10.1002/jhet.5570400521

  日期：2003.9

  Syntheses of several new 3,4-dihydropyrimidinones (DHPMs) on sodium sulfate solid support have been reported. The microwave enhanced rapid synthesis of the title compounds yielded a good percentage of the DHPMs. The catalytic activity of indium triflate enables to prepare a wide range of DHPMs. Syntheses of 2-hydroxyphenyl, 2-hydroxy-4-methoxyphenyl pendant groups on DHPMs scaffold are advantages of

  已有报道在硫酸钠固体载体上合成了几种新的3,4-二氢嘧啶酮（DHPM）。微波增强了标题化合物的快速合成，产生了很高百分比的DHPM。三氟甲磺酸铟的催化活性使得可以制备多种DHPM。DHPMs支架上的2-羟基苯基，2-羟基-4-甲氧基苯基侧基的合成是本方法的优势，非常易于环化，并且通过D 2 O交换研究证实了苯环上存在游离羟基。预计反应机理将通过吸收固体载体上的底物，然后通过In（OTf）3促进反应来进行 加上微波照射。