(S)-(+)-5-ethoxycarbonyl-6-methyl-4-(4-methylphenyl)-3,4-dihydropyrimidin-2(1H)-one | 854019-26-4

• 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: (S)-(+)-5-ethoxycarbonyl-6-methyl-4-(4-methylphenyl)-3,4-dihydropyrimidin-2(1H)-one
• 英文别名: (S)-5-ethoxycarbonyl-6-methyl-4-(p-tolyl)-3,4-dihydropyrimidin-2(1H)-one；ethyl (4S)-6-methyl-4-(4-methylphenyl)-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxylate
• CAS: 854019-26-4
• 化学式: C₁₅H₁₈N₂O₃
• 分子量: 274.32
• InChiKey: KTAAWYJATJFYRS-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  6-甲基-4-(4-甲基苯基)-2-氧代-3,4-二氢-1H-嘧啶-5-羧酸乙酯 在 tetraproline chiral stationary phase packed on HPLC column 作用下， 以 正己烷 、 异丙醇 为溶剂， 生成 (R)-5-ethoxycarbonyl-6-methyl-4-(4-methylphenyl)-3,4-dihydropyrimidin-2(1H)-one 、 (S)-(+)-5-ethoxycarbonyl-6-methyl-4-(4-methylphenyl)-3,4-dihydropyrimidin-2(1H)-one
  参考文献：
  名称：

  四脯氨酸手性固定相的溶液相合成和评价

  摘要：

  开发了一种协议方案，用于溶液相合成多克数量的两个9-芴基甲氧基羰基（Fmoc）保护的四脯氨酸肽。然后将这些四脯氨酸肽连接到氨基衍生的硅胶上。用三甲基乙酰基取代Fmoc基团会导致两个四脯氨酸手性固定相（CSP）。将这两种溶液相合成的四脯氨酸CSP与通过逐步固相合成制备的CSP的色谱行为进行比较，结果表明，这三种溶液均具有相似的色谱性能，可分离53种模型分析物。这表明寡聚脯氨酸的溶液相合成具有良好的批次重现性，选择器均质性以及可能的低成本等特定优势，是寡聚脯氨酸CSP固相合成的可行替代方法。手性，2012年。©2012 Wiley Periodicals，Inc.。

  DOI：

  10.1002/chir.22001

文献信息

• An Enantioselective Biginelli Reaction Catalyzed by a Simple Chiral Secondary Amine and Achiral Brønsted Acid by a Dual-Activation Route
  作者：Junguo Xin、Lu Chang、Zongrui Hou、Deju Shang、Xiaohua Liu、Xiaoming Feng

  DOI：10.1002/chem.200701581

  日期：2008.3.27

  An enantioselective Biginelli reaction that proceeds by a dual-activation route has been developed by using a combined catalyst of a readily available trans-4-hydroxyproline-derived secondary amine and a Bronsted acid. Aromatic, heteroaromatic, and fused-ring aldehydes were found to be suitable substrates for this multicomponent reaction. The corresponding dihydropyrimidines were obtained in moderate-to-good

  通过使用容易获得的反式4-羟基脯氨酸衍生的仲胺和布朗斯台德酸的组合催化剂，已经开发了通过双活化途径进行的对映选择性比吉内利反应。发现芳族，杂芳族和稠环醛是该多组分反应的合适底物。在温和条件下，以中等至良好的收率获得了相应的二氢嘧啶，收率高达98％ee。根据实验结果和观察到的产物的绝对构型，提出了一个合理的过渡态来解释激活和不对称诱导的起源。
• Highly Enantioselective Biginelli Reaction Promoted by Chiral Bifunctional Primary Amine-Thiourea Catalysts: Asymmetric Synthesis of Dihydropyrimidines
  作者：Yangyun Wang、Haitao Yang、Jipan Yu、Zhiwei Miao、Ruyu Chen

  DOI：10.1002/adsc.200900597

  日期：2009.12

  reaction was performed by using a combined catalyst consisting of a chiral bifunctional primary amine-thiourea 9f and a Brønsted acid with tert-butylammonium trifluoroacetate (t-BuNH2⋅TFA) as additive in dichloromethane at room temperature. The possible mechanism for the reaction has been proposed to explain the origin of the activation and the asymmetric induction.

  通过Biginelli反应，以中等至高收率（高达99％ee）实现了二氢嘧啶（DHPM）的非对映特异性形成。将反应物通过使用由手性双官能伯胺-硫脲的组合的催化剂进行9F和布朗斯台德酸与叔-butylammonium三氟乙酸盐（叔BuNH 2 ⋅TFA）在室温下在二氯甲烷中的添加剂。已经提出了反应的可能机理来解释活化和不对称诱导的起源。
• Primary Amine Catalyzed Biginelli Reaction for the Enantioselective Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones
  作者：Derong Ding、Cong-Gui Zhao

  DOI：10.1002/ejoc.201000448

  日期：——

  Several chiral primary amines, mainly those derived from the cinchona alkaloids, were evaluated as the organocatalysts for the asymmetric Biginelli reaction. With the quinine-derived amine catalyst 1 and after extensive optimization of the reaction conditions, 3,4-dihydropyrimidin-2(1H)-ones were obtained in moderate to good yields and 51-78% ee from a three-component reaction of aryl and aliphatic

  几种手性伯胺，主要来自金鸡纳生物碱，被评估为不对称 Biginelli 反应的有机催化剂。使用奎宁衍生的胺催化剂 1 和反应条件的广泛优化后，3,4-二氢嘧啶-2(1H)-酮以中等至良好的收率和 51-78% ee 从芳基的三组分反应中获得和脂肪醛、尿素和乙酰乙酸酯。
• Bifunctional primary amine-thiourea–TfOH (BPAT·TfOH) as a chiral phase-transfer catalyst: the asymmetric synthesis of dihydropyrimidines
  作者：Yangyun Wang、Jipan Yu、Zhiwei Miao、Ruyu Chen

  DOI：10.1039/c0ob01268h

  日期：——

  An enantioselective Biginelli reaction has been developed by using a bifunctional primary amine-thiourea–TfOH (BPAT·TfOH) as a chiral phase-transfer catalyst and t-BuNH2·TFA as an additive in saturated brine at room temperature. The corresponding dihydropyrimidines were obtained in moderate-to-good yields with up to 99% ee under mild conditions. A plausible transition state has been proposed to explain the origin of the activation and the asymmetric induction.

  在室温饱和盐水中，使用双功能伯胺-硫脲-TfOH（BPATÂ-TfOH）作为手性相转移催化剂和 t-BuNH2Â-TFA 作为添加剂，开发了一种对映体选择性 Biginelli 反应。在温和的条件下，得到了相应的二氢嘧啶，收率从中等到良好，ee高达 99%。研究人员提出了一种可信的过渡态来解释活化和不对称诱导的起源。
• Cooperative and Enantioselective NbCl5/Primary Amine Catalyzed Biginelli Reaction
  作者：Yong-Feng Cai、Hua-Meng Yang、Li Li、Ke-Zhi Jiang、Guo-Qiao Lai、Jian-Xiong Jiang、Li-Wen Xu

  DOI：10.1002/ejoc.201000894

  日期：2010.9

  evaluated in the Lewis acid/organocatalysts-based cooperative catalytic Biginelli reaction, which resulted in the determination of a novel cooperative Lewis acid/primary amine catalyst system, NbCl5/QN-NH2. The synergistic effect of NbCl5 and the quinine-derived primary amine is pronounced and gave dihydropyrimidiones (DHPMs) in moderate to good enantioselectivities (up to 84 % ee) and good to excellent yields

  在基于路易斯酸/有机催化剂的协同催化 Biginelli 反应中评估了一系列手性有机催化剂和路易斯酸，从而确定了一种新型的路易斯酸/伯胺协同催化剂体系 NbCl5/QN-NH2。NbCl5 和奎宁衍生的伯胺的协同作用是显着的，在温和的条件下以中等至良好的对映选择性（高达 84% ee）和良好至极好的产率（产率高达 99%）得到二氢嘧啶酮 (DHPM)。