ethyl 4-(4-methoxyphenyl)-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate | 380655-10-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: ethyl 4-(4-methoxyphenyl)-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate
• 英文别名: 4-(4-methoxyphenyl)-6-phenyl-5-ethoxycarbonyl-3,4-dihydropyrimidin-2(1H)-one；ethyl 4-methoxy-3,4-dihydropyrimidin-2(1H)-one-5-carboxylate；4-(4-Methoxyphenyl)-6-phenyl-5-ethoxy-carbonyl-3,4-dihydropyrimidin-2(1h)-one；ethyl 4-(4-methoxyphenyl)-2-oxo-6-phenyl-3,4-dihydro-1H-pyrimidine-5-carboxylate
• CAS: 380655-10-7
• 化学式: C₂₀H₂₀N₂O₄
• 分子量: 352.39
• InChiKey: NPYOUXKREMVCHM-UHFFFAOYSA-N

物化性质

• 熔点：
  162.5-163.5 °C(Solv: ethanol (64-17-5))
• 沸点：
  518.0±50.0 °C(Predicted)
• 密度：
  1.211±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-(4-methoxyphenyl)-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate 在 硝酸 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.58h， 生成 ethyl 1-[(4-acetylphenyl)methyl]-4-(4-methoxyphenyl)-2-oxo-6-phenyl-pyrimidine-5-carboxylate
  参考文献：
  名称：

  Synthesis of dihydropyrimidine α,γ-diketobutanoic acid derivatives targeting HIV integrase

  摘要：

  The synthesis and antiviral evaluation of a series of dihydropyrimidinone and thiopyrimidine derivatives bearing aryl alpha, gamma-diketobutanoic acid moiety are described using the Biginelli multicomponent reaction as key step. The most active among 20 synthesized novel compounds were 4c, 4d and 5b, which possess nanomolar HIV-1 integrase (IN) stand transfer (ST) inhibition activities. In order to understand their mode of interactions within the IN active site, we docked all the compounds into the previously reported X-ray crystal structure of IN. We observed that compounds 4c, 4d and 5b occupied an area close to the two catalytic Mg2+ ions surrounded by their chelating triad (E221, D128 and D185), DC16, Y212 and the beta-diketo acid moiety of 4c, 4d and 5b chelating Mg2+. As those compounds lack anti-HIV activities in cell, their prodrugs were synthetized. The prodrug 4c' exhibited an anti-HIV activity of 0.19 mu M in primary human lymphocytes with some cytotoxicity. All together, these results indicate that the new analogs potentially interact within the catalytic site with highly conserved residues important for IN catalytic activity. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.09.015
• 作为产物：
  描述：

  phenyl [(p-metoxyphenyl)(tosyl)methyl]carbamate 在 ammonium hydroxide 、 sodium hydride 、 对甲苯磺酸 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 6.0h， 生成 ethyl 4-(4-methoxyphenyl)-2-oxo-6-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate
  参考文献：
  名称：

  A new approach to the synthesis of Biginelli compounds

  摘要：

  A new synthesis of 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid esters is based on the reactions of alpha-tosyl-substituted phenyl carbamates with the enolates of beta-oxoesters followed by treatment with ammonia and dehydration of the resulting 4-hydroxyhexahydropyrimidin-2-ones.

  DOI：

  10.1070/mc2005v015n02abeh002022

文献信息

• Selective acylation of 5-nitro- and 5-ethoxycarbonyl-4,6-diaryl-3,4-dihydropyrimidin-2(1H)-ones
  作者：V. F. Sedova、O. P. Shkurko

  DOI：10.1134/s1070428010110163

  日期：2010.11

  The acetylation and chloroacetylation of 5-nitro- and 5-ethoxycarbonyl-substituted 4,6-diaryl-3,4-dihydropyrimidin-2(1H)-ones proceeds regioselectively at the N3 atom of the heterocycle whereas the acetylation of the 5-aryloxy-substituted analog results in a mixture of N1- and N3-acetylated regioisomers.

  5-硝基和5-乙氧基羰基取代的4,6-二芳基-3,4-二氢嘧啶-2（1 H）-ones的乙酰化和氯乙酰化在杂环的N 3原子上区域选择性地进行，而5的乙酰化-芳氧基取代的类似物产生N 1-和N 3-乙酰化的区域异构体的混合物。
• An unusual oxidation–dealkylation of 3,4-dihydropyrimidin-2(1H)-ones mediated by Co(NO3)2·6H2O/K2S2O8 in aqueous acetonitrile
  作者：Pachaiyappan Shanmugam、Paramasivan T. Perumal

  DOI：10.1016/j.tet.2006.11.010

  日期：2007.1

  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.
• Regioselective dehydrogenation of 3,4-dihydropyrimidin-2(1H)-ones mediated by ceric ammonium nitrate
  作者：P. Shanmugam、P.T. Perumal

  DOI：10.1016/j.tet.2006.07.063

  日期：2006.10

  Ceric ammonium nitrate (CAN) has been explored for the regioselective oxidation of 3,4-dihydropyrimidin-2(1H)-ones (DHPMs). Interestingly, we obtained ethyl 2,4-dioxo-6-phenyl-tetrahydropyrimidin-5-carboxylates as the major products during the oxidation of DHPMs by CAN/AcOH at 80 degrees C. The reaction afforded a mixture of products while employing CAN in organic solvents without additives. However, the regioselective dehydrogenated product, ethyl 6-methyl-4-aryl(alkyl)-pyrimidin-2(1H)-one-5-carboxylate was obtained by performing the reaction with NaHCO3. The single crystal X-ray crystallography of ethyl 6-methyl-4-(2-phenyl)-pyrimidin-2(1H)-one-5-carboxylate revealed that the oxidized product existed in amidic form rather than aromatized enol form of pyrimidines. The efficiency of the present protocol enabled the synthesis of structurally diverse pyrimidines in moderate to good yields under milder reaction conditions. (c) 2006 Elsevier Ltd. All rights reserved.
• Synthesis of dihydropyrimidine α,γ-diketobutanoic acid derivatives targeting HIV integrase
  作者：Ozkan Sari、Vincent Roy、Mathieu Métifiot、Christophe Marchand、Yves Pommier、Stéphane Bourg、Pascal Bonnet、Raymond F. Schinazi、Luigi A. Agrofoglio

  DOI：10.1016/j.ejmech.2015.09.015

  日期：2015.11

  The synthesis and antiviral evaluation of a series of dihydropyrimidinone and thiopyrimidine derivatives bearing aryl alpha, gamma-diketobutanoic acid moiety are described using the Biginelli multicomponent reaction as key step. The most active among 20 synthesized novel compounds were 4c, 4d and 5b, which possess nanomolar HIV-1 integrase (IN) stand transfer (ST) inhibition activities. In order to understand their mode of interactions within the IN active site, we docked all the compounds into the previously reported X-ray crystal structure of IN. We observed that compounds 4c, 4d and 5b occupied an area close to the two catalytic Mg2+ ions surrounded by their chelating triad (E221, D128 and D185), DC16, Y212 and the beta-diketo acid moiety of 4c, 4d and 5b chelating Mg2+. As those compounds lack anti-HIV activities in cell, their prodrugs were synthetized. The prodrug 4c' exhibited an anti-HIV activity of 0.19 mu M in primary human lymphocytes with some cytotoxicity. All together, these results indicate that the new analogs potentially interact within the catalytic site with highly conserved residues important for IN catalytic activity. (C) 2015 Elsevier Masson SAS. All rights reserved.
• A new approach to the synthesis of Biginelli compounds
  作者：Anatoly D. Shutalev、Nikolay N. Kurochkin

  DOI：10.1070/mc2005v015n02abeh002022

  日期：2005.1

  A new synthesis of 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid esters is based on the reactions of alpha-tosyl-substituted phenyl carbamates with the enolates of beta-oxoesters followed by treatment with ammonia and dehydration of the resulting 4-hydroxyhexahydropyrimidin-2-ones.