ethyl 4-((3-bromophenyl)(methyl)amino)-3-oxobutanoate | 1364822-77-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: ethyl 4-((3-bromophenyl)(methyl)amino)-3-oxobutanoate
• 英文别名: ethyl 4-(3-bromo-N-methylanilino)-3-oxobutanoate
• CAS: 1364822-77-4
• 化学式: C₁₃H₁₆BrNO₃
• 分子量: 314.179
• InChiKey: KPZOVJQAGYJYJO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 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-((3-bromophenyl)(methyl)amino)-3-oxobutanoate 在 肼 作用下， 以 乙醇 为溶剂， 生成 5-[(3-bromo-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 、 3-溴-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73%的产率得到ethyl 4-((3-bromophenyl)(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

• 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.
• 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.