ethyl 6-methyl-2-oxo-4-(4-(trifluoromethyl) phenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 6-methyl-2-oxo-4-(4-(trifluoromethyl) phenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate
• 英文别名: ethyl 6-methyl-2-oxo-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate；ethyl 6-methyl-4-(4-trifluoromethylphenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate；5-(ethoxycarbonyl)-6-methyl-4-(4-(trifluoromethyl)phenyl)-3,4-dihydropyrimidin-2(1H)-one；5-(ethoxycarbonyl)-6-methyl-4-(4-trifluoromethylphenyl)-3,4-dihydropyrimidin-2(1H)-one；3,4-dihydro-5-ethoxycarbonyl-4-(4-trifluoromethylphenyl)-6-methylpyrimidine-2(1H)-one；4-(p-trifluoromethylphenyl)-5-ethoxycarbonyl-6-methyl-3,4-dihydropyrimidin-2-(1H)-one；Ethyl 6-methyl-2-oxo-4-[4-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate；ethyl 6-methyl-2-oxo-4-[4-(trifluoromethyl)phenyl]-3,4-dihydro-1H-pyrimidine-5-carboxylate
• 化学式: C₁₅H₁₅F₃N₂O₃
• 分子量: 328.291
• InChiKey: OFLFPNJNGFZVLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-(三氟甲基)苄醇 在 二甲基亚砜 、 1-丙基磷酸酐 作用下， 以 乙酸乙酯 为溶剂， 反应 7.75h， 生成 ethyl 6-methyl-2-oxo-4-(4-(trifluoromethyl) phenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate
  参考文献：
  名称：

  T3P®-DMSO介导的一锅串联方法，从醇中合成3,4-二氢嘧啶-2（1H）-酮/硫酮

  摘要：

  背景：Biginelli反应是最重要的多组分化学反应之一，可产生3,4-dihydropyrimidin-2（1H）-ones。尽管有一个世纪以来使用不同的底物报道了Biginelli反应的报道，但文献中仍缺乏使用醇作为底物的例子。迄今为止，尚未探索用另一官能团取代醛组分。 方法：在本研究中，我们已使用丙基膦酸酐（T3P®）-DMSO作为从芳香族醇一锅合成3,4-二氢嘧啶-2（1H）-酮/硫酮的高效温和试剂。 结果：在温和的条件下，醇被原位氧化为醛，然后与β-酮酸酯和脲/硫脲进行三组分反应，生成3,4-二氢嘧啶-2（1H）-1 /硫酮。 结论：首次在温和的反应条件下以良好的收率首次从醇类直接合成3,4-二氢嘧啶-2（1H）-酮/硫酮。操作简便，成本低廉，试剂毒性小是该方案的主要优点。

  DOI：

  10.2174/1570178614666170720115044

文献信息

• One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues
  作者：Jessica Bais、Fabio Benedetti、Federico Berti、Iole Cerminara、Sara Drioli、Maria Funicello、Giorgia Regini、Mattia Vidali、Fulvia Felluga

  DOI：10.3390/molecules25184152

  日期：——

  A library of dihydropyrimidinones was synthesized via a “one-pot” three component Biginelli reaction using different aldehydes in combination with β-dicarbonyl compounds and urea. Selected 2-thiooxo and 2-imino analogs were also obtained with the Biginelli reaction from thiourea and guanidine hydrochloride, respectively. The products were screened in vitro for their β-secretase inhibitory activity. The majority of the compounds resulted to be active, with IC50 in the range 100 nM–50 μM.

  通过使用不同的醛与β-二羰基化合物和尿素的“一锅法”三组分Biginelli反应合成了一系列二氢嘧啶酮类化合物。选择性地，也从硫脲和盐酸胍得到了2-硫氧代和2-亚氨基类似物。这些产物在体外被筛选，用于评估它们的β-分泌酶抑制活性。大多数化合物表现出活性，IC50在100 nM至50 μM范围内。
• Organocatalytic Application of Ionic Liquids: [bmim][MeSO4] as a Recyclable Organocatalyst in the Multicomponent Reaction for the Preparation of Dihydropyrimidinones and -thiones
  作者：Asit Chakraborti、Sudipta Roy、Pradeep Jadhavar、Kapileswar Seth、Kulin Sharma

  DOI：10.1055/s-0030-1260067

  日期：2011.7

  substitution in the latter. The ionic liquid can be recovered and reused for five consecutive reactions without significant loss of catalytic efficiency. The applicability of the methodology for large-scale reaction highlights its potential for bulk synthesis. ionic liquid - organocatalyst - multicomponent reaction - dihydropyrimidinone - dihydropyrimidinethione

  已经研究了基于1-丁基-3-甲基咪唑鎓的室温离子液体的有机催化潜力，该反应通过单锅多组分反应（包括醛，β-酮酸酯或β-二酮）合成二氢嘧啶酮和-硫酮，尿素或硫脲在短时间内的收率很高。研究了影响离子液体作为催化剂效率的因素，例如阴离子和咪唑鎓阳离子，特别是后者中C2取代的影响。可以回收离子液体并将其重新用于五个连续的反应，而不会显着降低催化效率。该方法用于大规模反应的适用性突出了其本体合成的潜力。 离子液体-有机催化剂-多组分反应-二氢嘧啶酮-二氢嘧啶硫酮
• Propane phosphonic acid anhydride: a new promoter for the one-pot Biginelli synthesis of 3,4-dihydropyrimidin-2(1H)-ones
  作者：Franz L. Zumpe、Melanie Flüß、Krischan Schmitz、Andreas Lender

  DOI：10.1016/j.tetlet.2006.12.098

  日期：2007.2

  Propane phosphonic acid anhydride has been found to promote the Biginelli synthesis of 3,4-dihydropyrimidin-2(1H)-ones. The use of this agent is characterized by moderate costs, low toxicity and simple workup conditions.

  已发现丙烷膦酸酐可促进3,4-二氢嘧啶-2（1 H）-one的Biginelli合成。该试剂的使用具有成本适中，毒性低和后处理条件简单的特点。
• Parallel synthesis of dihydropyrimidinones using Yb(III)-resin and polymer-supported scavengers under solvent-free conditions. A green chemistry approach to the Biginelli reaction
  作者：Alessandro Dondoni、Alessandro Massi

  DOI：10.1016/s0040-4039(01)01728-2

  日期：2001.11

  An efficient synthesis of an array of 3,4-dihydropyrimidin-2-(1H)-ones using solid-supported ytterbium(III) reagent from aldehydes, 1,3-dicarbonyl compounds and urea (Biginelli reaction) under solvent-free conditions is described. Purification of each member of the library was carried out using a cocktail of acid and basic polymer-supported scavengers

  在无溶剂的条件下，由醛，1,3-二羰基化合物和脲（Biginelli反应）使用固载（III）试剂高效合成3,4-二氢嘧啶-2-（1 H）-酮阵列描述。使用酸和碱性聚合物支持的清除剂的混合物对文库的每个成员进行纯化
• Li(glycine)(CF₃SO₃) as an effective and recoverable catalyst for the preparation of 3,4-dihydropyrimidine-2-(1H)-one under solvent-free conditions
  作者：Esmayeel Abbaspour-Gilandeh、Seyyedeh Cobra Azimi、Aidin Mohammadi-Barkchai

  DOI：10.1039/c4ra07334g

  日期：——

  An efficient solvent-free protocol for the synthesis of 3,4-dihydropyrimidine-2-(1H)-one by the one-pot condensation of aldehyde, ethyl acetoacetate and urea using Li(glycine)(CF3SO3) as a reusable acidic ionic liquid is reported. These reactions have the advantages in this work of clean reaction, simple purification, short reaction time and high yields.

  报道了一种高效的无溶剂合成3,4-二氢嘧啶-2-(1H)-酮的方法，该方法通过使用Li(glycine)(CF3SO3)作为可重复使用的酸性离子液体，在一个反应器中将醛、乙酰乙酸乙酯和尿素进行缩合。这些反应在本工作中具有反应干净、纯化简单、反应时间短及产率高的优点。