4-(4-羟基苯基)-6-甲基-2-氧代-1,2,3,4-四氢嘧啶-5-羧酸乙酯 | 123629-41-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4-(4-羟基苯基)-6-甲基-2-氧代-1,2,3,4-四氢嘧啶-5-羧酸乙酯
• 英文名称: 5-ethoxycarbonyl-6-methyl-4-(4-hydroxyphenyl)-3,4-dihydropyrimidin-2(1H)-one
• 英文别名: 5-(ethoxycarbonyl)-4-(4-hydroxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one；ethyl 4-(4-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate；ethyl 4-(4-hydroxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one-5-carboxylate；ethyl 1,2,3,4-tetrahydro-4-(4-hydroxyphenyl)-6-methyl-2-oxopyrimidine-5-carboxylate；5-ethoxycarbonyl-6-methyl-4-(4-hydroxyphenyl)-3,4-dihydropyrimidine-2(1H)-one；ethyl 4-(4-hydroxyphenyl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxylate
• CAS: 123629-41-4
• 化学式: C₁₄H₁₆N₂O₄
• 分子量: 276.292
• InChiKey: PRLATGWSLBXBHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 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：

  4-(4-羟基苯基)-6-甲基-2-氧代-1,2,3,4-四氢嘧啶-5-羧酸乙酯 在 水 、 sodium hydroxide 、 盐酸 作用下， 以 水 为溶剂， 反应 4.0h， 以68%的产率得到(E)-4-(4-hydroxy-phenyl)-6-(4-hydroxystyryl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid
  参考文献：
  名称：

  Computer simulation of the in vitro and in vivo anti-inflammatory activities of dihydropyrimidines acid derivatives through the inhibition of cyclooxygenase-2

  摘要：

  Simulation of virtually designed 20 compounds as COX-2 inhibitors using molecular modelling of protein-ligand interactions to predict drug structure-activity relationship was performed in this study. A synthetic route with a rational chemical approach to (E)-2-oxo-(thio)-4-substituted phenyl-6-styryl-1,2,3,4-tetrahydro-pyrimidine-5-caboxylic acid was designed and demonstrated. A comparative analysis of antimetabolite drug and corresponding metabolites (virtually designed compounds) provided a better understanding of rational drug design. COX-1(pdb entry: 1eqg) and COX-2(pdb entry: 6cox) enzymes docked with novel ligands were evaluated for binding energies. Lead optimization was performed by computational simulation: methoxy-substituted analogues displayed the highest negative ligand-protein-binding energies. These results prompted us to evaluate in vivo anti-inflammatory activity by carrageenan-induced paw oedema test in rats at a dose of 100 mg/kg. Ibuprofen was administered as standard drug. Lead compounds having significant activity were tested for in vitro cyclooxygenase isoenzyme inhibition assay and found to be more selective towards COX-2 as indicated by COX-2 selective index. The objective of our research is to accept the challenge of discovery of new drug. To ensure the desired target specificity and potency, bioavailability and lack of toxicity, our approach stems out lead generation from virtual screening to their synthesis and ends up with biological assays.

  DOI：

  10.1007/s00044-012-0244-2
• 作为产物：
  描述：

  对羟基苯甲醛 在 sodium hydrogensulfite 、 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 反应 12.0h， 生成 4-(4-羟基苯基)-6-甲基-2-氧代-1,2,3,4-四氢嘧啶-5-羧酸乙酯
  参考文献：
  名称：

  使用可回收王树脂负载的磺酸催化剂从醛亚硫酸氢盐加合物高效合成 3,4-二氢-2(1H)-嘧啶酮

  摘要：

  ：使用可回收聚合物负载的磺酸催化剂，从醛亚硫酸氢盐加合物、乙酰乙酸乙酯和尿素开发了一种高效的一锅多组分合成 3,4-二氢嘧啶-2(1H)-酮。与以前的合成方法相比，这种新方法提供了几个优势，包括高产率、商业上可行、最少的后处理操作和可持续的化学实践。

  DOI：

  10.2174/1570178618666210225113723

文献信息

• Concentrated solar radiation as a renewable heat source for a preparative-scale and solvent-free Biginelli reaction
  作者：Yatin U. Gadkari、Navnath T. Hatvate、Balaram S. Takale、Vikas N. Telvekar

  DOI：10.1039/d0nj01351j

  日期：——

  A well-known Biginelli reaction for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones was performed in an environmentally responsible manner. Large numbers of substrates were screened, and found to give excellent yields of the desired products. In addition to the synthesis of drug molecules, the reaction was easily scaled up to 50 mmol. The present method was also energy efficient and saved

  以对环境负责的方式进行了众所周知的Biginelli反应，该反应用于合成3,4-二氢嘧啶-2（1 H）-酮/硫酮。筛选了大量的底物，发现得到所需产物的优异产率。除了合成药物分子外，该反应还容易扩大到50 mmol。与传统方法相比，本方法还具有能源效率，并节省了95％以上的能量。
• Synthesis and comparing the antibacterial activities of pyrimidine derivatives
  作者：B ANDREWS、K KOMATHI、S MOHAN

  DOI：10.1007/s12039-017-1228-z

  日期：2017.3

  series of 10 derivatives of 5-(5-amino-1,3,4-thiadiazole-2-yl)-3,4-dihydro-6-methyl-4-phenyl-pyrimidin-2(1H)-one and 10 derivatives of 3,4-dihydro-5-(5-mercapto-4H-1,2,4-triazol-3-yl)-6-methyl-4-phenyl pyrimidin-2(1H)-one have been synthesized. Among the synthesized derivatives, triazole substituted compounds have shown higher antibacterial inhibition when compared to the thiadiazole derivatives. All the

  5-（5-氨基-1,3,4-噻二唑-2-基）-3,4-二氢-6-甲基-4-苯基-嘧啶-2（1 H）-的10种衍生物已合成10，3,4-二氢-5-（5-巯基-4H-1,2,4-三唑-3-基）-6-甲基-4-苯基嘧啶-2（1 H）-的衍生物。在合成的衍生物中，与噻二唑衍生物相比，三唑取代的化合物显示出更高的抗菌抑制作用。通过IR，1 H和13 C NMR，GC-MS和CHN分析表征了新合成化合物的所有结构。与标准药物环丙沙星相比，大多数化合物已显示出令人鼓舞的抗菌活性。 5-（5-氨基-1,3,4-噻二唑-2-基）-3,4-二氢-6-甲基-4-苯基嘧啶-2（1 H）-的十个衍生物系列和十个衍生物3,4-二氢-5-（5-巯基-4H-1,2,4-三唑-3-基）-6-甲基-4-苯基嘧啶-2（1 H）-的合成及结构表征。在合成的衍生物中，与噻二唑衍生物相比，三唑取代的化合物显示出更高的抗菌抑制作用。
• A New Biginelli Reaction Procedure Using Potassium Hydrogen Sulfate as the Promoter for an Efficient Synthesis of 3,4-Dihydropyrimidin-2(1<i>H</i>)-one
  作者：Shujiang Tu、Fang Fang、Songlei Zhu、Tuanjie Li、Xiaojing Zhang、Qiya Zhuang

  DOI：10.1055/s-2004-815419

  日期：——

  conditions have been found to carry out the Biginelli reaction for the synthesis of 3,4-dihydropyrimidin-2(1H)-one derivatives. This synthesis was performed using potassium hydrogen sulfate as the promoter in glycol solution. Compared with the classical Biginelli reaction conditions, this new method has the advantage of excellent yields (85-99%) and short reaction time (0.5-2 h).

  已经发现简单和改进的条件可以进行 Biginelli 反应以合成 3,4-二氢嘧啶-2(1H)-one 衍生物。该合成是在乙二醇溶液中使用硫酸氢钾作为促进剂进行的。与经典的 Biginelli 反应条件相比，这种新方法具有收率高（85-99%）和反应时间短（0.5-2 h）的优点。
• A One-Pot Synthesis of 3,4-Dihydropyrimidin-2-(1H)-ones from Primary Alcohols Promoted by Bi(NO3)3·5H2O in Two Different Media: Organic Solvent and Ionic Liquid
  作者：Ahmad Reza Khosropour、Ahmad R. Khosropour、Mohammd M. Khodaei、Mojtaba Beygzadeh、Mahbubeh Jokar

  DOI：10.3987/com-04-10257

  日期：——

  A new, simple and efficient procedure for the one-pot conversion of alcohols instead of aldehydes to the corresponding 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) with Bi(NO 3 ) 3 .5H 2 O as a commercially available, inexpensive, stable and non-toxic reagent in two media, acetonitrile (as an organic solvent) and tetrabutylammonium bromide (as an ionic liquid) is described. This one-pot oxidation-cyclocondensation

  一种新的、简单且有效的方法，用于将醇而不是醛一锅转化为相应的 3,4-二氢嘧啶-2(1H)-酮 (DHPM)，其中 Bi(NO 3 ) 3 .5H 2 O 作为商业应用描述了在乙腈（作为有机溶剂）和四丁基溴化铵（作为离子液体）这两种介质中可获得、廉价、稳定和无毒的试剂。这种一锅氧化-环缩合反应无需分离任何中间体（醛）即可进行，从而缩短了时间，节省了能源和原材料。另一方面，用这种新的一锅法处理伯醇产生的脱氢嘧啶酮的产率高于传统方法中的产率。
• A facile approach for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones using a microwave promoted Biginelli protocol in ionic liquid
  作者：ABHISHEK N DADHANIA、VAIBHAV K PATEL、DIPAK K RAVAL

  DOI：10.1007/s12039-012-0278-5

  日期：2012.7

  recycled and reused in at least six subsequent reactions with consistent activity. Carboxy functionalized ionic liquid [cmmim][BF4] is shown to be an efficient and green catalyst for the one pot synthesis of 3,4-dihydropyrimidin-2-(1H)-ones heterocycles under microwave irradiation. This methodology represents an easy access to Biginelli compounds with high yields and purity. The ionic liquid was recycled

  羧基官能化的离子液体[cmmim] [BF 4 ]已被证明是在微波辐射下一锅合成3,4-二氢嘧啶-2-（1 H）-一个杂环的高效绿色催化剂。离子液体微波策略可以轻松获得具有高收率和纯度的Biginelli化合物。发现该方案与不同结构上不同的醛相容。离子液体被循环使用，并在至少六个随后的具有一致活性的反应中重新使用。 羧基官能化的离子液体[cmmim] [BF 4 ]被证明是在微波辐射下一锅合成3,4-二氢嘧啶-2-（1 H）-ones杂环的高效绿色催化剂。这种方法论代表了容易获得高收率和高纯度的比吉内利化合物的方法。离子液体被回收利用，结果一致。