1,3,6-trimethyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester | 67092-74-4

• 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-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester
• 英文别名: ethyl 1,2,3,4-tetrahydro-1,3,6-trimethyl-2-oxo-4-phenylpyrimidine-5-carboxylate；ethyl 1,3,6-trimethyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate；ethyl 1,3,6-trimethyl-2-oxo-4-(phenyl)-3,4-dihydropyrimidine-5-carboxylate；5-ethoxycarbonyl-1,3,6-trimethyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one；1,3,6-trimethyl-2-oxo-4-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester；5-Ethoxycarbonyl-1,6-trimethyl-4-phenyl-3,4-dihydropyrimidin-2(1H)one；ethyl 1,3,6-trimethyl-2-oxo-4-phenyl-4H-pyrimidine-5-carboxylate
• CAS: 67092-74-4
• 化学式: C₁₆H₂₀N₂O₃
• 分子量: 288.346
• InChiKey: GEKSXCGZMRSDHW-UHFFFAOYSA-N

物化性质

• 熔点：
  97 °C(Solv: dichloromethane (75-09-2))
• 沸点：
  402.0±45.0 °C(Predicted)
• 密度：
  1.141±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 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-2-oxo-4-phenyl-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 6-((4-((2,4-dioxothiazolidin-5-ylidene)methyl)phenoxy)methyl)-1,3-dimethyl-2-oxo-4-phenyl-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 、 苯甲醛 在 ammonium cerium (IV) nitrate 作用下， 以 neat (no solvent) 为溶剂， 反应 0.03h， 以96%的产率得到1,3,6-trimethyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester
  参考文献：
  名称：

  N，N'-二烷基-4-芳基-3,4-二氢嘧啶酮和亚硫醚：硝酸铈铈铵的催化合成及X射线晶体学测定的分子结构

  摘要：

  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。

  DOI：

  10.1002/jhet.2735

文献信息

• Metalation of Biginelli Compounds. A General Unprecedented Route to C-6 Functionalized 4-Aryl-3,4-dihydropyrimidinones
  作者：Kamaljit Singh、Sukhdeep Singh、Aman Mahajan

  DOI：10.1021/jo050675q

  日期：2005.7.1

  4-Aryl-6-methyl-3,4-dihydro-2(1H)-pyrimidinone esters (DHPMs) readily undergo metalation at the C-6 methyl (vinylogous ester) position on treatment with lithium diisopropylamide at −10 °C. The resulting anion intermediates can be treated with electrophilic reagents to afford functionalized DHPMs that have been chemically elaborated mainly at the C-6 position. Di- and trianion formation is also possible

  在-10°C下用二异丙基氨基锂处理时，4-芳基-6-甲基-3,4-二氢-2（1 H）-嘧啶酮酯（DHPM）易于在C-6甲基（乙烯基酯）位置发生金属化。可以用亲电试剂处理所得的阴离子中间体，以提供功能化的DHPM，该功能化的DHPM主要在C-6位置进行了化学修饰。当用过量当量的碱进行反应时，在乙烯基的甲基和NH位置也可能形成二阴离子和三阴离子。
• Highly Efficient Synthesis of Substituted 3,4-Dihydropyrimidin-2-(1H)-ones (DHPMs) Catalyzed by Hf(OTf)4: Mechanistic Insights into Reaction Pathways under Metal Lewis Acid Catalysis and Solvent-Free Conditions
  作者：Rui Kong、Shuai-Bo Han、Jing-Ying Wei、Xiao-Chong Peng、Zhen-Biao Xie、Shan-Shan Gong、Qi Sun

  DOI：10.3390/molecules24020364

  日期：——

  catalytic activity of Group IVB transition metal Lewis acids, Hf(OTf)4 was identified as a highly potent catalyst for ”one-pot, three-component” Biginelli reaction. More importantly, it was found that solvent-free conditions, in contrast to solvent-based conditions, could dramatically promote the Hf(OTf)4-catalyzed formation of 3,4-dihydro-pyrimidin-2-(1H)-ones. To provide a mechanistic explanation, we closely

  在我们对 IVB 族过渡金属路易斯酸催化活性的研究中，Hf(OTf)4 被确定为“一锅三组分”Biginelli 反应的高效催化剂。更重要的是，发现与基于溶剂的条件相比，无溶剂条件可以显着促进 Hf(OTf)4 催化的 3,4-二氢-嘧啶-2-(1H)-酮的形成。为了提供机理解释，我们以“顺序双分子缩合”和“一锅三组分”方式仔细研究了 Hf(OTf)4 对所有三种潜在反应途径的催化作用。实验结果表明，无溶剂条件和 Hf(OTf)4 催化的协同作用不仅通过增强亚胺路线和激活烯胺路线大大加速了 Biginelli 反应，而且避免了 Knoevenagel 加合物的形成，这可能导致不需要的副产品。此外，乙酰乙酸甲酯在 MeOH-d4 中的 HD 交换反应的 1H-MMR 示踪表明 Hf(IV) 阳离子可能显着加速酮-烯醇互变异构化并激活 β-酮部分，从而有助于整体反应速率。
• 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。
• Separation of enantiomers of 4-aryldihydropyrimidines by direct enantioselective HPLC. A critical comparison of chiral stationary phases
  作者：Oliver P. Kleidernigg、C.Oliver Kappe

  DOI：10.1016/s0957-4166(97)00214-0

  日期：1997.6

  The separation of the enantiomers of 29 racemic 4-aryldihydropyrimidine-5-carboxylates (DHPMs), aza-analogs of nifedipine-type dihydropyridine calcium channel modulators, was evaluated in direct enantioselective HPLC, employing the following commercially available chiral stationary phases (CSPs): Chiralcel OD-H, ChiraDex, Chirobiotic V and T, and Whelk-O1. In addition, a 1,2-diphenyl-1,2-diaminoethane based CSP and two quinine carbamate based chiral ion exchangers were also employed. For all 29 DHPMs separation of individual enantiomers could be achieved with at least one CSP with alpha-values ranging from 1.10 to 8.67. (C) 1997 Elsevier Science Ltd.
• N1-Alkylated 3,4-dihydropyrimidine-2(1H)-ones: Convenient one-pot selective synthesis and evaluation of their calcium channel blocking activity
  作者：Kamaljit Singh、Divya Arora、Elizabeth Poremsky、Jazmyne Lowery、Robert S. Moreland

  DOI：10.1016/j.ejmech.2008.10.002

  日期：2009.5

  It has been found that selective N1-alkylation of 3,4-dihydropyrimidine-2(1H)-ones can be achieved under solvent-less, mild phase transfer catalytic (PTC) conditions with tetrabutylammonium hydrogen sulfate and 50% aqueous NaOH as the catalyst and base, respectively. The procedure is tolerant to substitutional variation at key diversity points on the pyrimidinone moiety. (C) 2008 Elsevier Masson SAS All rights reserved.