6-(溴甲基)-2-氧代-4-苯基-1,2,3,4-四氢嘧啶-5-羧酸乙酯 | 14758-00-0

• 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: 6-(溴甲基)-2-氧代-4-苯基-1,2,3,4-四氢嘧啶-5-羧酸乙酯
• 英文名称: ethyl 6-(bromomethyl)-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate
• 英文别名: ethyl 6-bromomethyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate；6-bromomethyl-5-ethoxycarbonyl-4-phenyl-3,4-dihydro-2(1H)-pyrimidinone；ethyl 6-bromomethylene-4-phenyl-pyrimidin-2(1H)-one-5-carboxylate；6-bromomethyl-5-ethoxycarbonyl-4-phenyl-3,4-dihydropyrimidinone；6-bromomethyl-2-oxo-4-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester；2-Oxo-5-ethoxycarbonyl-6-brommethyl-4-phenyl-1,2,3,4-tetrahydro-pyrimidin；ethyl 6-(bromomethyl)-2-oxo-4-phenyl-3,4-dihydro-1H-pyrimidine-5-carboxylate
• CAS: 14758-00-0
• 化学式: C₁₄H₁₅BrN₂O₃
• mdl: MFCD00591303
• 分子量: 339.189
• InChiKey: OVFDHKGBFHKINA-UHFFFAOYSA-N

物化性质

• 沸点：
  426.2±45.0 °C(Predicted)
• 密度：
  1.432±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.285
• 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：

  6-(溴甲基)-2-氧代-4-苯基-1,2,3,4-四氢嘧啶-5-羧酸乙酯 在 六甲基磷酰三胺 、 sodium azide 作用下， 反应 72.0h， 以72%的产率得到ethyl (+/-)-6-(azidomethyl)-1,2,3,4-tetrahydro-2-oxo-4-phenyl-5-pyrimidinecarboxylate
  参考文献：
  名称：

  Kappe, Oliver C., Liebigs Annalen der Chemie, 1990, # 5, p. 505 - 507

  摘要：

  DOI：
• 作为产物：
  描述：

  乙酰乙酸乙酯 在 硫酸 、 溴 、 甲烷 作用下， 以 正己烷 、 氯仿 、 乙腈 为溶剂， 反应 12.0h， 生成 6-(溴甲基)-2-氧代-4-苯基-1,2,3,4-四氢嘧啶-5-羧酸乙酯
  参考文献：
  名称：

  3,4-二氢嘧啶-2-(1H)一基Calix[4]芳烃作为抗菌剂和激酶抑制剂的合成、体外和分子对接研究

  摘要：

  如今，杯[n]芳烃被用作完全开发的合成支架，其在结构基团中提供多种空间排列，这使得它们更足以用作连接其他重要衍生物（如二氢嘧啶酮化合物）的床。最近，基于杯芳烃化合物的二氢嘧啶衍生物的开发和识别引起了极大的兴趣。本研究成功合成了一系列由四叔丁基杯[4]芳烃下缘与3,4-二氢嘧啶-2-(1H)-酮连接而成的衍生物。这是通过 6-溴甲基-DHPM 化合物 (5a-d) 和四叔丁基杯[4]芳烃之间的反应实现的。合成的化合物显示出抗菌和抗真菌活性。在这些化合物中，化合物e表现出最强的抗菌作用。关于抗真菌活性的结果表明，合成的化合物，特别是化合物c，在根除人类真菌病原体方面具有显着的有效性，并在本研究中显示出有希望的性能。此外，对这些化合物进行了分子对接研究，揭示了新型衍生物 d 和 e 具有独特的化学结构，可作为 EGFR 突变体的高效抑制剂。

  DOI：

  10.1016/j.molstruc.2024.138597

文献信息

• The Thorpe–Ziegler-type reaction of 3-cyanopyridine-2(1H)-thiones with Biginelli 6-bromomethyl-3,4-dihydropyrimidin-2(1H)-ones: cascade assembling of tetra- and pentacyclic heterocyclic scaffolds
  作者：Iryna O. Lebedyeva、Victor V. Dotsenko、Vladimir V. Turovtsev、Sergey G. Krivokolysko、V'yacheslav M. Povstyanoy、Mikhaylo V. Povstyanoy

  DOI：10.1016/j.tet.2012.09.041

  日期：2012.11

  3-Cyanopyridine-2(1H)-thiones have been shown to react with Biginelli-type ethyl 4-aryl-6-(bromomethyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates upon heating in DMF giving rise to ethyl 4-aryl-6-[(3-cyanopyridin-2-yl)thio]methyl}-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates. The latter upon treatment with an excess of NaH or t-BuOK in boiling DMF undergo a tandem Thorpe–Ziegler-type

  已经显示3-氰基吡啶-2（1 H）-硫酮在加热时与Biginelli型4-芳基-6-（溴甲基）-2-氧-1,2,3,4-四氢嘧啶-5-羧酸乙酯反应在DMF中，生成4-芳基-6-[（（3-氰基吡啶-2-基）硫基]甲基] -2-氧代-1,2,3,4-四氢嘧啶-5-羧酸乙酯。后者在沸腾的DMF中用过量的NaH或t- BuOK处理后，进行串联的Thorpe–Ziegler型杂环化反应，得到吡啶并[3″，2″：4'，5'] thieno [2'，3'：5 ，6]吡啶[4,3- d ]嘧啶衍生物，收率高。测试所选化合物的抗菌和抗真菌活性。
• Pyrimidines as block units in heterocycles: novel synthesis of pyrimidines and condensed pyrimidine derivatives
  作者：Wesam S. Shehab、Mohamed G. Assy、Hamed Y. Moustafa、Magda H. Abdellattif、Hamdi M. A. Rahman

  DOI：10.1007/s13738-019-01712-4

  日期：2019.11

  Bromopyrimidine 15 transformed into thiazolopyrimidine 17. Cyclization of bromomethyl pyrimidine 15 resulted in imidazolopyrimidine 19. Upon reacting the compound 15 with ammonium acetate resulted in amination affording the amino derivative 20. Oxazolopyrimidine 21 was obtained as the result of the reaction of compound 1 with chloroacetic acid and p-nitrobenzaldehyde. Compound 21 was transformed into pyridopyrimidine

  化合物1与苯甲醛缩合产生苯乙烯基嘧啶2。吡啶并嘧啶5，8和10导致从[4 + 2]环加成的（缩聚）1与丙二腈，氰基乙酸乙酯和/或乙酰乙酸乙酯。化合物1还通过多步反应（水解，氯化，异硫氰酸酯形成和分子内环化）与吡啶并嘧啶14一致。溴嘧啶15转化为噻唑并嘧啶17。溴甲基嘧啶15的环化反应生成咪唑并嘧啶19。使化合物15与乙酸铵反应后，胺化得到氨基衍生物20。作为化合物1与氯乙酸和对硝基苯甲醛反应的结果，获得了恶唑并嘧啶21。当分别与氰基乙酰胺和/或苯肼反应时，化合物21被转化为25型的嘧啶嘧啶23和吡啶嘧啶。所有测试的化合物对病原微生物，尤其是吡啶嘧啶衍生物21均显示出良好的微生物活性。
• Synthesis of 6-styryldihydropyrimidinones and 6-styryldihydropyridinones via the respective 6-alkylphosphonates
  作者：Rufus Smits、Sergey Belyakov、Marina Petrova、Vladislav Kozhich、Ruslan Muhamadejev

  DOI：10.1007/s10593-023-03145-7

  日期：2022.12

  with 6-bromomethyl-3,4-dihydropyrimidin-2(1H)-one or analogous 6-bromomethyl-3,4-dihydropyridin-2(1H)-one provided the respective 6-alkylphosphonates in excellent yields. The heterocyclic alkylphosphonates are useful synthons in the Horner–Wadsworth–Emmons reaction for introducing a styryl moiety. Bromination of 6-methyl-4-phenyl-3,4-dihydropyridin-2(1H)-one with NBS in methanol resulted in an unexpected

  Arbuzov 反应中的亚磷酸三甲酯或三乙酯与 6-溴甲基-3,4-二氢嘧啶-2(1 H )-一或类似的 6-溴甲基-3,4-二氢吡啶-2(1 H )-一提供相应的 6-烷基膦酸盐以优异的收率。杂环烷基膦酸酯是 Horner-Wadsworth-Emmons 反应中用于引入苯乙烯基部分的有用合成子。在甲醇中用 NBS溴化 6-methyl-4-phenyl-3,4-dihydropyridin-2(1 H )-one 得到意想不到的化合物，而在氯仿中用溴溴化得到预期的 6-bromomethyl-3,4- dihydropyridin-2(1 H )-one，容易进行亲核取代。中间体和产物通过单晶X射线衍射验证。
• 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.