ethyl 4-((4-chlorophenyl)(methyl)amino)-3-oxobutanoate | 1364822-73-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: ethyl 4-((4-chlorophenyl)(methyl)amino)-3-oxobutanoate
• 英文别名: ethyl 4-(4-chloro-N-methylanilino)-3-oxobutanoate
• CAS: 1364822-73-0
• 化学式: C₁₃H₁₆ClNO₃
• 分子量: 269.728
• InChiKey: MAVRTMOMVHMZIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-((4-chlorophenyl)(methyl)amino)-3-oxobutanoate 在 肼 作用下， 以 乙醇 为溶剂， 生成 5-[(4-chloro-N-methylanilino)methyl]-1,2-dihydropyrazol-3-one
  参考文献：
  名称：

  Arylazanylpyrazolone Derivatives as Inhibitors of Mutant Superoxide Dismutase 1 Dependent Protein Aggregation for the Treatment of Amyotrophic Lateral Sclerosis

  摘要：

  The arylsulfanylpyrazolone and aryloxanylpyrazolone scaffolds previously were reported to inhibit Cu/Zn superoxide dismutase 1 dependent protein aggregation and to extend survival in the ALS mouse model. However, further evaluation of these compounds indicated weak pharmacokinetic properties and a relatively low maximum tolerated dose. On the basis of an ADME analysis, a new series of compounds, the arylazanylpyrazolones, has been synthesized, and structure-activity relationships were determined. The SAR results showed that the pyrazolone ring is critical to cellular protection. The NMR, IR, and computational analyses suggest that phenol-type tautomers of the pyrazolone ring are the active pharmacophore with the arylazanylpyrazolone analogues. A comparison of experimental and calculated IR spectra is shown to be a valuable method to identify the predominant tautomer.

  DOI：

  10.1021/jm400079a
• 作为产物：
  描述：

  4-氯乙酰乙酸乙酯 、 4-氯-N-甲基苯胺 在 碳酸氢钠 、 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以85%的产率得到ethyl 4-((4-chlorophenyl)(methyl)amino)-3-oxobutanoate
  参考文献：
  名称：

  Direct Amination of γ-Halo-β-ketoesters with Anilines

  摘要：

  The direct amination of alpha-haloacetoacetates with anilines is described. Compared to existing methods, this simple protocol provides an attractive strategy to prepare diverse gamma-anilino-beta-ketoesters in one step. Good to excellent yields of the amination products were obtained under robust conditions, providing versatile and useful scaffolds.

  DOI：

  10.1021/jo300239e

文献信息

• One-pot synthesis of 4-pyrimidone-2-thioether through base/acid-mediated condensation of <i>S</i>-alkylisothiourea and β-ketoester
  作者：Zhichao Lu、Tsung-Yun Wong、Yonghong Gan、Guihui Chen、Dinesh J. Paymode、Cheng-yi Chen

  DOI：10.1039/d4ra00039k

  日期：——

  4-Pyrimidone-2-thioethers can be useful synthetic precursors to densely functionalized pyrimidines, commonly encountered in bioactive molecules. A convenient one-pot access to 4-pyrimidone-2-thioethers is reported herein, which utilizes a sequential base- and acid-mediated condensation of alkylisothioureas with β-ketoesters. Owing to mild reaction conditions, good to excellent functional group tolerance

  4-嘧啶酮-2-硫醚可作为生物活性分子中常见的密集功能化嘧啶的有用合成前体。本文报道了一种方便的一锅法获得4-嘧啶酮-2-硫醚的方法，其利用烷基异硫脲与β-酮酯的顺序碱和酸介导的缩合。由于反应条件温和，可实现良好至优异的官能团耐受性和产率。该方法的实用性通过 200 克规模的关键阿达格拉西中间体的合成得到了证明。
• α-Diazo β-Keto Ester as Precursor to Aromatic CH Insertion and Wolff Rearrangement with Different Directing Groups
  作者：Biao Ma、Fang-Lei Chen、Xing-Yu Xu、Yi-Nan Zhang、Li-Hong Hu

  DOI：10.1002/adsc.201300763

  日期：2014.2.10

  AbstractA tunable aromatic CH insertion and a Wolff rearrangement of α‐diazo β‐keto esters precursor were developed. Different directing groups on nitrogen led with high selectivity to either dihydroquinoline or 2‐carbamoylacrylate motifs, which can be transformed to multiple heterocyclic scaffolds.magnified image
• Arylazanylpyrazolone Derivatives as Inhibitors of Mutant Superoxide Dismutase 1 Dependent Protein Aggregation for the Treatment of Amyotrophic Lateral Sclerosis
  作者：Yinan Zhang、Radhia Benmohamed、He Huang、Tian Chen、Cindy Voisine、Richard I. Morimoto、Donald R. Kirsch、Richard B. Silverman

  DOI：10.1021/jm400079a

  日期：2013.3.28

  The arylsulfanylpyrazolone and aryloxanylpyrazolone scaffolds previously were reported to inhibit Cu/Zn superoxide dismutase 1 dependent protein aggregation and to extend survival in the ALS mouse model. However, further evaluation of these compounds indicated weak pharmacokinetic properties and a relatively low maximum tolerated dose. On the basis of an ADME analysis, a new series of compounds, the arylazanylpyrazolones, has been synthesized, and structure-activity relationships were determined. The SAR results showed that the pyrazolone ring is critical to cellular protection. The NMR, IR, and computational analyses suggest that phenol-type tautomers of the pyrazolone ring are the active pharmacophore with the arylazanylpyrazolone analogues. A comparison of experimental and calculated IR spectra is shown to be a valuable method to identify the predominant tautomer.
• Direct Amination of γ-Halo-β-ketoesters with Anilines
  作者：Yinan Zhang、Richard B. Silverman

  DOI：10.1021/jo300239e

  日期：2012.4.6

  The direct amination of alpha-haloacetoacetates with anilines is described. Compared to existing methods, this simple protocol provides an attractive strategy to prepare diverse gamma-anilino-beta-ketoesters in one step. Good to excellent yields of the amination products were obtained under robust conditions, providing versatile and useful scaffolds.