1,3,6-trimethyl-4-(4-chlorophenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester | 302934-94-7

• 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: 1,3,6-trimethyl-4-(4-chlorophenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester
• 英文别名: ethyl 4-(4-chlorophenyl)-1,2,3,4-tetrahydro-1,3,6-trimethyl-2-oxopyrimidine-5-carboxylate；ethyl 4-(4-chlorophenyl)-1,3,6-trimethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate；ethyl 4-(4-chlorophenyl)-1,3,6-trimethyl-2-oxo-4H-pyrimidine-5-carboxylate
• CAS: 302934-94-7
• 化学式: C₁₆H₁₉ClN₂O₃
• 分子量: 322.791
• InChiKey: GDFQTVWDXLPLDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,3,6-trimethyl-4-(4-chlorophenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester 在 哌啶 、 溴 、 potassium carbonate 、 potassium iodide 作用下， 以 乙醇 、 氯仿 、 乙腈 为溶剂， 反应 24.0h， 生成 ethyl 4-(4-chlorophenyl)-6-((4-((2,4-dioxothiazolidin-5-ylidene)methyl)phenoxy) methyl)-1,3-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
  参考文献：
  名称：

  Synthesis, in-vitro α-glucosidase inhibition, antioxidant, in-vivo antidiabetic and molecular docking studies of pyrrolidine-2,5-dione and thiazolidine-2,4-dione derivatives

  摘要：

  alpha-Glucosidase is considered as a therapeutic target for the treatment of type 2 diabetes mellitus (DM2). In current study, we synthesized pyrrolidine-2,5-dione (succinimide) and thiazolidine-2,4-dione derivatives and evaluated for their ability to inhibit alpha-Glucosidase. Pyrrolidine-2,5-dione derivatives (11a-o) showed moderate to poor alpha-glucosidase inhibition. Compound 11o with the IC50 value of 28.3 +/- 0.28 mu M emerged as a good inhibitor of alpha-glucosidase. Thiazolidine-2,4-dione and dihydropyrimidine (TZD-DHPM) hybrids (22a-c) showed excellent inhibitory activities. The most active compound 22a displayed IC50 value of 0.98 +/- 0.008 mu M. Other two compounds of this series also showed activity in low micromolar range. The in-vivo antidiabetic study of three compounds 11n, 11o and 22a were also determined using alloxan induced diabetes mice model. Compounds 11o and 22a showed significant hypoglycemic effect compared to the reference drug. In-vivo acute toxicity study showed the safety of these selected compounds. In-silico docking studies were carried out to rationalize the in-vitro results. The binding modes and bioassay results of TZD-DHPM hybrids showed that interactions with important residues appeared significant for high potency.

  DOI：

  10.1016/j.bioorg.2019.103128
• 作为产物：
  描述：

  1,3-二甲基脲 、 乙酰乙酸乙酯 、 4-氯苯甲醛 在 一水合硫酸镁 作用下， 以 水 为溶剂， 反应 7.0h， 以60%的产率得到1,3,6-trimethyl-4-(4-chlorophenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester
  参考文献：
  名称：

  硫酸碱金属（II）环保工艺的发展促进了N，N'-二甲基取代的（未取代的）-4-芳基-3,4-二氢嘧啶酮（硫酮）和相应的双类似物在水性介质中的合成：绿色化学指标

  摘要：

  在水性介质中，将不同的碱金属（II）硫酸盐用作N，N'-二甲基取代的和未取代的4-芳基-3,4-二氢嘧啶酮（硫酮）及其相应的双类似物的催化剂。在各种盐中，MgSO 4 ·7H 2 O（泻盐）被证明是最好的催化剂，以良好至极佳的收率提供了所需的产物。该催化剂能够构建一系列化合物库，特别是对于N，N'-二甲基取代的DHPM，其合成在文献中非常罕见。通过绿色化学的应用评估了在多种底物上的反应指标和非常好的相关性。J.杂环化​​学.2010。

  DOI：

  10.1002/jhet.283

文献信息

• <i>N,N′</i>-Dialkyl-4-Aryl-3,4-Dihydropyrimidinones and Thiones: Ceric Ammonium Nitrate Catalyzed Synthesis and Molecular Structure Determination by X-ray Crystallography
  作者：Chingrishon Kathing、Sushil Kumar、Shokip Tumtin、Nongthombam Geetmani Singh、Jims World Star Rani、Ridaphun Nongrum、Rishanlang Nongkhlaw

  DOI：10.1002/jhet.2735

  日期：2017.3

  This work presents a microwave assisted solvent‐free synthesis of N,N′‐dialkyl‐4‐aryl‐3,4‐dihydropyrimidinones/thiones in the presence of Ceric Ammonium Nitrate (CAN) via direct condensation of aromatic aldehydes, β‐keto ester, and N,N′‐dialkylurea/thiourea. The highlights of the methodology adopted are (i) facile condensation of the reactants into product without any side‐products, and (ii) short

  这项工作提出了在硝酸铈铵（CAN）存在下通过芳族醛，β-酮酸酯的直接缩合在微波辅助下无溶剂合成N，N'-二烷基-4-芳基-3,4-二氢嘧啶酮/硫酮的方法，以及N，N'-二烷基脲/硫脲。所采用方法的重点是：（i）反应物易于缩合为无任何副产物的产物；（ii）反应时间短，产率高，纯度高。所有合成的化合物都通过光谱技术（例如FTIR，1 H NMR，13 C NMR和Mass）进行了表征和建立。该化合物的结构通过单晶X射线衍射分析得到了进一步证实。
• Efficient synthesis of 3,4-dihydropyrimidin-2-ones in low melting tartaric acid–urea mixtures
  作者：Sangram Gore、Sundarababu Baskaran、Burkhard Koenig

  DOI：10.1039/c1gc00009h

  日期：——

  A general, efficient and green method for the synthesis of dihydropyrimidinones is described under mild conditions employing low melting mixtures of L-(+)-tartaric acid and urea derivatives as a novel reaction medium. The melt plays a triple role: as solvent, as catalyst and as reactant, furnishing highly functionalized dihydropyrimidinones in good to excellent yields.

  本文描述了一种在温和条件下合成二氢嘧啶酮的通用、高效且环保的方法，该方法采用L-(+)-酒石酸和尿素衍生物的低熔点混合物作为新型反应介质。熔体具有三重作用：作为溶剂、催化剂和反应物，以良好至极佳的收率提供高官能化的二氢嘧啶酮。