ethyl 4,6-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate | 17994-56-8

• 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: ethyl 4,6-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
• 英文别名: 5-ethoxycarbonyl-4,6-dimethyl-3,4-dihydropyrimidin-2(1H)-one；4,6-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester；4,6-Dimethyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester；ethyl 4,6-dimethyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxylate
• CAS: 17994-56-8
• 化学式: C₉H₁₄N₂O₃
• mdl: MFCD01793559
• 分子量: 198.222
• InChiKey: JFHAMNVZHGKQDQ-UHFFFAOYSA-N

物化性质

• 熔点：
  189-190 °C
• 沸点：
  280.9±40.0 °C(Predicted)
• 密度：
  1.111±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.555
• 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：

  ethyl 4,6-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 在 吡啶 、 四(三苯基膦)钯 、 硝酸 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 17.34h， 生成 ethyl 4,6-dimethyl-2-(o-tolyl)pyrimidine-5-carboxylate
  参考文献：
  名称：

  Exploiting the Biginelli reaction: nitrogen-rich pyrimidine-based tercyclic α-helix mimetics

  摘要：

  Several rationally designed pyrimidine-based scaffolds intended to mimic the spatial projection of the i, i+3, and i+7 residues of an alpha-helix and also possess improved aqueous solubility were prepared. A Biginelli-oxidation process was used to form the central pyrimidine ring of these scaffolds, which was subsequently manipulated to form pyrimidine-based tercyclic alpha-helix mimetics. A pyrimidine-based scaffold designed to mimic the alpha-helical BH3 domain of the pro-apoptotic Bak protein was also prepared as a putative inhibitor of the BcI-x(L)/Bak protein-protein interaction. The pyrimidine-based tercyclic alpha-helix mimetics, and the putative Bcl-x(L) inhibitor, were assessed using a luminescence competition assay, however, none displayed inhibitory activity against Bel-x(L) or Mcl-1. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2015.12.044
• 作为产物：
  描述：

  4,6-dimethyl-2-oxo-1,2-dihydropyrimidine-5-carboxylic acid ethyl ester 在 碘 、 magnesium 作用下， 以 甲醇 为溶剂， 反应 26.0h， 以70%的产率得到ethyl 4,6-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
  参考文献：
  名称：

  镁/甲醇：一种化学选择性还原嘧啶-2（1 H）-ones的有效还原剂

  摘要：

  甲醇中的镁是化学选择性还原嘧啶2（1 H）-ones的有效试剂。其他可还原的官能团，例如烯胺酯和乌里多羰基的酯和烯烃，不受影响。这构成了通过嘧啶-2（1 H）-one的还原形成Biginelli 3,4-dihydropyrimidin-2（1 H）one的第一个例子。

  DOI：

  10.1016/j.tetlet.2009.02.165

文献信息

• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR
  申请人：Arvinas, Inc.

  公开号：US20180099940A1

  公开（公告）日：2018-04-12

  The present disclosure relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor.

  本公开涉及双功能化合物，其用于降解和（抑制）雄激素受体。具体而言，本公开涉及包含一端结合到E3泛素连接酶的谷氨酰腺苷环配体，另一端结合到雄激素受体的部分的化合物，使得雄激素受体与泛素连接酶靠近，以实现雄激素受体的降解（和抑制）。本公开展示了与根据本公开涉及的化合物相关的广泛的药理活性范围，与雄激素受体的降解/抑制一致。
• An expedient protocol of the Biginelli dihydropyrimidine synthesis using carbonyl equivalents
  作者：Kamaljit Singh、Jasbir Singh、Prasant K. Deb、Harjit Singh

  DOI：10.1016/s0040-4020(99)00760-7

  日期：1999.10

  A one - pot condensation of perhydro-1,3 heterocycles - aldehyde equivalents with ethyl acetoacetate and ureas provides a convenient synthesis of the title compounds with a variety of substituents at C-4. Yields are equivalent or significantly higher than the conventional methods.

  全氢-1,3杂环-醛当量与乙酰乙酸乙酯和脲的一锅缩合反应可方便地合成标题化合物，其在C-4处具有多个取代基。产率与常规方法相当或相当高。
• Unprecedented single-pot protocol for the synthesis of N1, C6-linked bicyclic 3,4-dihydropyrimidinones via lithiation of Biginelli compounds
  作者：Kamaljit Singh、Sukhdeep Singh

  DOI：10.1016/j.tet.2008.10.001

  日期：2008.12

  4-Aryl/alkyl-6-methyl-3,4-dihydropyrimidin-2(1H)-one ester derivatives readily undergo metalation at the C6 methyl (vinylogous ester) position along with two acidic NHs upon treatment with n-butyllithium at −10 °C. The trianion of DHPMs thus obtained react smoothly with various terminal dibromoalkanes to afford N1, C6-linked bicyclic DHPM derivatives, which represent key structural features of the

  4-芳基/烷基-6-甲基-3,4-二氢-2（1 H ^） -酮酯衍生物时容易治疗经历在C6甲基（插烯酯）的位置与金属化两个酸性NHS沿Ñ在丁基锂- 10°C。如此获得的DHPM的三阴离子可与各种末端二溴代烷烃平稳反应，以提供N1，C6连接的双环DHPM衍生物，这些衍生物代表了具有药效的海洋生物碱如batzelladine A和crambescin A的关键结构特征。
• Selective N1-Alkylation of 3,4-Dihydropyrimidin-2(1<i>H</i>)-ones Using Mitsunobu-Type Conditions
  作者：C. Oliver Kappe、Doris Dallinger

  DOI：10.1055/s-2002-34881

  日期：——

  The regioselective N1-alkylation of 3,4-dihydropyrimidin-2(1H)-ones via Mitsunobu reaction is reported. Using the highly reactive Mitsunobu coupling reagent combination N,N,N′,N′-tetramethylazodicarboxamide/tributylphosphine (TMAD-TBP) and a set of primary alcohols a small library of N1-alkylated dihydropyrimidones is obtained in good to excellent yields.

  报道了通过 Mitsunobu 反应实现 3,4-二氢嘧啶-2(1H)-酮的 N1-烷基选择性烷基化。使用高活性的 Mitsunobu 偶联试剂组合 N,N,N',N'-四甲基偶氮二羧酰胺/三丁基膦（TMAD-TBP）以及一系列伯醇，获得了产率良好至优异的一系列 N1-烷基化二氢嘧啶酮的小型化合物库。
• Polyphosphate Ester-Mediated Synthesis of Dihydropyrimidines. Improved Conditions for the Biginelli Reaction
  作者：C. Oliver Kappe、S. Fabio Falsone

  DOI：10.1055/s-1998-1764

  日期：1998.7

  Dihydropyrimidines 7 are prepared in high yield by a one-pot condensation of aldehydes, acetoacetates, and ureas using a polyphosphate ester-mediated cyclocondensation reaction. Yields are significantly higher than utilizing classical Biginelli reaction conditions.

  二氢嘧啶7通过醛、乙酰乙酸酯和脲在一锅法中使用聚磷酸酯介导的环缩合反应，以高产率制备。与传统的Biginelli反应条件相比，产率显著提高。