4-(2-fluoro-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester | 301193-43-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-(2-fluoro-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester
• 英文别名: (±)-ethyl 4-(2-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate；ethyl 4-(2-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate；5-(ethoxycarbonyl)-6-methyl-4-(2-fluorophenyl)-3,4-dihydropyrimidin-2(1H)-one；4-(o-fluorophenyl)-5-ethoxycarbonyl-6-methyl-3,4-dihydropyrimidin-2-(1H)-one；5-ethoxycarbonyl-6-methyl-4-(2-fluorophenyl)-3,4-dihydropyrimidin-2-(1H)-one；5-ethoxycarbonyl-4-(2-fluorophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one；ethyl 4-(2-fluorophenyl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxylate
• CAS: 301193-43-1
• 化学式: C₁₄H₁₅FN₂O₃
• 分子量: 278.283
• InChiKey: FFIQTJURIHEMLK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 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：
  67.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2-fluoro-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester 在 硫酸 、 一水合肼 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 3.0h， 生成 4-(2-fluorophenyl)-6-methyl-N'-(2-nitrobenzylidene)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carbohydrazide
  参考文献：
  名称：

  Synthesis and biological evaluation of 1,3,4-oxadiazole bearing dihydropyrimidines as potential antitubercular agents

  摘要：

  A series of 5-(4-acetyl-5-(aryl)-4,5-dihydro-1,3,4-oxadiazol-2-yl)-4-(2-fluorophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-ones (4a-l) were synthesized in very good yields (56-78 %). Biginelli adduct 1 synthesized in the first step was reacted with hydrazine hydrate to furnish carbohydrazide intermediate 2 which on further reaction with different aryl aldehydes yielded 4-(2-fluorophenyl)-6-methyl-N'-(aryl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carbohydrazides (3a-l). These intermediates 3a-l were cyclized with the help of acetic anhydride to give the titled compounds 4a-l. All the newly synthesized compounds 4a-l were screened for their in vitro antitubercular activity against Mycobacterium tuberculosis H(37)Rv (Mtb) using Lowenstein-Jensen method. Compounds 4c, 4f, 4h, 4i and 4j inhibited more than 90 % of mycobacterial growth. Minimum inhibitory concentration (MIC) for compound 4i was found to be equipotent (MIC: 0.20 mu g/ml) to the reference drug isoniazid. Structure activity relationship revealed that the presence of electron withdrawing group/atoms at para position of phenyl ring remarkably enhanced the antitubercular activity of synthesized compounds.

  DOI：

  10.1007/s00044-015-1485-7
• 作为产物：
  描述：

  乙酰乙酸乙酯 、 2-氟苯甲醛 、 尿素 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88%的产率得到4-(2-fluoro-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester
  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

• Air‐stable zirconium (IV)‐salophen perfluorooctanesulfonate as a highly efficient and reusable catalyst for the synthesis of 3,4‐dihydropyrimidin‐2‐(1H)‐ones/thiones under solvent‐free conditions
  作者：Ningbo Li、Yijun Wang、Feijun Liu、Xin Zhao、Xinhua Xu、Quan An、Keming Yun

  DOI：10.1002/aoc.5454

  日期：2020.3

  An air‐stable complex of zirconium (IV)‐salophen perfluorooctanesulfonate (1) was successfully synthesized by reacting Zr (salphen)Cl2 and C8F17SO3Ag. Complex 1 was characterized and studied by different techniques (NMR, IR, HRMS, TG‐DSC, conductivity and acidity measurements), and was found to be air‐stable, water tolerant, thermally stable and strongly Lewis‐acidic. Complex 1 exhibited high catalytic

  通过使Zr（salphen）Cl 2与C 8 F 17 SO 3 Ag反应成功合成了一种空气稳定的锆（IV）-salophen全氟辛烷磺酸盐（1）。配合物1通过不同的技术（NMR，IR，HRMS，TG-DSC，电导率和酸度测量）进行了表征和研究，被发现具有空气稳定性，耐水性，热稳定性和强路易斯酸性。络合物1在无溶剂条件下通过醛，1,3-二羰基化合物和脲/硫脲的Biginelli反应合成3,4-二氢嘧啶-2-（1H）-酮/硫酮具有很高的催化效率。此外，复数1可以重复使用5次，而催化效率的变化却很小。与以前报道的方法相比，该方案的重要特征是无溶剂条件，反应时间短，底物相容性广，效率高和可重复使用性好。
• Air-stable Organobismuth(V) Bisperfluorooctanesulfonate as an Efficient Catalyst for the Synthesis of N-Containing Compounds
  作者：Penghui Wang、Jinying Wang、Chak-Tong Au、Renhua Qiu、Xinhua Xu、Shuang-Feng Yin

  DOI：10.1002/adsc.201500998

  日期：2016.4.14

  Triphenyl bismuth bisperfluorooctanesulfonate is an air‐ and water‐stable Lewis acid. It exhibits high catalytic efficiency for the synthesis of nitrogen heterocycles such as diindolylmethane derivatives, dihydropyrimidinones, dihydropyridines and 1,2‐disubstitued benzimidazoles under mild condition. Furthermore, it can be reused without loss of activity in a test of five cycles.This catalytic system

  三全氟辛烷磺酸三苯基铋是一种对空气和水稳定的路易斯酸。在温和条件下，它对合成氮杂环（如二吲哚基甲烷衍生物，二氢嘧啶酮，二氢吡啶和1,2-二取代的苯并咪唑）具有很高的催化效率。此外，在五个周期的测试中，它可以重复使用而不会失去活性。该催化体系为合成含氮化合物提供了一种简单而有效的方法。
• Acridone-pyrimidine hybrids- design, synthesis, cytotoxicity studies in resistant and sensitive cancer cells and molecular docking studies
  作者：Manikanta Murahari、Karanam Vanitha Prakash、Godefridus J. Peters、YC Mayur

  DOI：10.1016/j.ejmech.2017.08.023

  日期：2017.10

  have identified 11a, 11b, 11d and 11h as potential inhibitors. Molecular docking studies identified the orientation and binding interactions at the active site of Akt1 and DNA. Compounds 12e and 12f have shown good cytotoxicity profile against lung cancer cell lines of sensitive and resistant type. Acute toxicity study of compound 12f at the dose of 5000 mg/kg has identified no signs of clinical toxicity

  设计具有取代的嘧啶的a啶酮的杂化系统，其目的是发现靶向癌细胞中多种机制的下一代抗癌药。通过实验室中简便的方法合成了杂合化合物，并通过NMR和质谱方法进行了表征，并筛选了针对A549（肺癌），Hela（宫颈），MCF7（乳腺癌）和MDA-MB-231（乳腺癌）细胞的细胞毒性线。化合物对细胞增殖的评估可鉴定出活性化合物11b，11d和11h对抗MCF7，MDA-MB-231和A549细胞系。用CT-DNA进行进一步的吸收滴定和凝胶电泳确定，杂化分子部分通过DNA嵌入显示出抗癌活性。用Akt激酶进行的蛋白质印迹分析的其他结果还表明，杂合化合物具有抑制Akt激酶活性并诱导凋亡的能力，而ABCC1则表明活性化合物也具有调节与ABCC1 / MRP1相关的多药耐药性（MDR）的能力。选择性Akt1激酶测定已确定11a，11b，11d和11h为潜在抑制剂。分子对接研究确定了Akt1和DNA活性位点的方向
• New Efficient Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones Catalyzed by Benzotriazolium-Based Ionic Liquids under Solvent-Free Conditions
  作者：Zhiqing Liu、Rong Ma、Dawei Cao、Chenjiang Liu

  DOI：10.3390/molecules21040462

  日期：——

  An efficient synthesis of novel 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) and their derivatives, using Brønsted acidic ionic liquid [C2O2BBTA][TFA] as a catalyst, from the condensation of aryl aldehyde, β-ketoester and urea was described. Reactions proceeded smoothly for 40 min under solvent-free conditions and gave the desirable products with good to excellent yields (up to 99%). The catalyst could

  使用 Brønsted 酸性离子液体 [C2O2BBTA][TFA] 作为催化剂，从芳醛、β-酮酯和尿素进行了描述。反应在无溶剂条件下顺利进行 40 分钟，得到所需的产物，产率良好至极好（高达 99%）。催化剂可以很容易地回收和重复使用，至少六次循环具有相似的效率。
• Exploring the influence of the substituent at position 4 in a series of 3,4-dihydropyrimidin-2(1H)-one A2B adenosine receptor antagonists
  作者：Abel Crespo、Abdelaziz El Maatougui、Jhonny Azuaje、Luz Escalante、María Majellaro、María Isabel Loza、José Brea、María Isabel Cadavid、Hugo Gutiérrez-de-Terán、Eddy Sotelo

  DOI：10.1007/s10593-017-2054-4

  日期：2017.3

  identify selective adenosine A2B receptor antagonists, we have obtained a focused library of 4-substituted 3,4-dihydropyrimidin-2(1H)-ones and its affinity for the four human adenosine receptor subtypes was determined. The synthesis was accomplished by using an experimentally simple and efficient Biginelli approach. The biological evaluation of the library revealed that all the documented derivatives exhibit

  在鉴定选择性腺苷A2B受体拮抗剂的计划的背景下，我们获得了一个4位取代的3,4-二氢嘧啶-2（1 H）-ones的库，并确定了其对四种人腺苷受体亚型的亲和力。该合成是通过使用实验简单有效的Biginelli方法完成的。对文库的生物学评估表明，所有已记录的衍生物对A 2B受体的亲和力均较低或可忽略不计，因此突出了3,4-二氢嘧啶-2（1 H）-一种化学型中4位取代基的至关重要性。。