(E)-N-tert-butyl-4-(4-chlorophenyl)-2-oxobut-3-enamide | 1320256-69-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-N-tert-butyl-4-(4-chlorophenyl)-2-oxobut-3-enamide
• CAS: 1320256-69-6
• 化学式: C₁₄H₁₆ClNO₂
• 分子量: 265.74
• InChiKey: CWPYQUUSMUILJG-RMKNXTFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-N-tert-butyl-4-(4-chlorophenyl)-2-oxobut-3-enamide 在 bis(1,5-cyclooctadiene)diiridium(I) dichloride 、 C₃₂H₃₇FeN₂OP 、 氢气 、 potassium hydroxide 作用下， 以 1,2-二氯乙烷 、 异丙醇 为溶剂， 20.0 ℃ 、2.03 MPa 条件下， 反应 12.0h， 以98%的产率得到(S,E)-N-(tert-butyl)-4-(4-chlorophenyl)-2-hydroxybut-3-enamide
  参考文献：
  名称：

  铱/f-Amphox 催化的苯乙烯基乙醛酰胺的不对称氢化

  摘要：

  我们报告了用于制备手性高苯丙氨酸衍生物的铱催化不对称氢化反应。在铱/f-amphox 络合物的催化下，苯乙烯基乙醛酰胺的不对称氢化顺利进行，转化率高达 10,000，ee 高达 98%。该方法已成功应用于苯那普利片段的合成，这是一种用于治疗高血压的药物。

  DOI：

  10.1055/s-0037-1609623
• 作为产物：
  描述：

  (E)-N-(tert-butyl)-4-(4-chlorophenyl)-2-hydroxybut-3-enamide 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 生成 (E)-N-tert-butyl-4-(4-chlorophenyl)-2-oxobut-3-enamide
  参考文献：
  名称：

  铑催化的β，γ-不饱和α-酮酰胺的不对称芳基化反应，用于构建非外消旋的γ，γ-二芳基羰基化合物

  摘要：

  本文描述了使用简单的新手性亚磺酰基膦配体将高区域和对映体选择性的铑催化的1,4-芳基硼酸加成到β，γ-不饱和α-酮酰胺上的方法。这种转化为构建手性非外消旋的γ，γ-二芳基取代的羰基化合物提供了一种有吸引力的方法，如舍曲林和四氢喹啉-2-羧酰胺的简明合成中所举例说明的那样。

  DOI：

  10.1002/anie.201403325

文献信息

• Enantioselective Copper-Catalyzed Conjugate Addition of Trimethylaluminum to β,γ-Unsaturated α-Ketoamides: Efficient Access to γ-Methyl-Substituted Carbonyl Compounds
  作者：Sylvie Goncalves-Contal、Ludovic Gremaud、Alexandre Alexakis

  DOI：10.1002/anie.201306541

  日期：2013.11.25

  4‐adducts were obtained with perfect 1,4‐regioselectivity and good to excellent yields and ee values. The potential synthetic utility of the methodology was highlighted by preparation of γ‐methyl‐substituted carbonyls, key synthons to many natural products. binap=2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl, TC=thiophene carboxylate.

  完美图片：通过使用三甲基铝试剂和β，γ-不饱和α-酮酰胺，可获得1,4-加合物，具有完美的1,4-区域选择性，并具有极佳的收率和ee 值。通过制备γ-甲基取代的羰基化合物（许多天然产物的关键合成子），突出了该方法的潜在合成效用。binap = 2,2'-双（二苯基膦基）-1,1'-联萘基，TC =噻吩羧酸盐。
• Synthesis and biological evaluation of α-ketoamides as inhibitors of the Dengue virus protease with antiviral activity in cell-culture
  作者：Christian Steuer、Christian Gege、Wolfgang Fischl、Karl H. Heinonen、Ralf Bartenschlager、Christian D. Klein

  DOI：10.1016/j.bmc.2011.05.015

  日期：2011.7

  The development of small molecule inhibitors of the viral protease is of considerable interest for the treatment of emergent flaviviral diseases such as Dengue or West Nile fever. Until today little progress has been made in finding drug-like compounds that inhibit the protease and provide a starting point for lead optimization. We describe here the initial steps of a drug discovery effort that focused on the styryl pharmacophore, combined with a ketoamide function to serve as electrophilic trap for the catalytic serine. This resulted in a fragment-like lead compound with reasonable target affinity and good ligand efficiency, which was extensively modified to explore structure-activity relationships. Selected compounds were cross-tested against the West Nile virus protease and thrombin, indicating that selectivity for one or more flaviviral proteases can be achieved. Finally, the antiviral activity of several protease inhibitors was confirmed in a cell-culture model of Dengue virus replication. The SAR presented here may serve as starting point for further drug discovery efforts with the aim of targeting flaviviral proteases. (C) 2011 Elsevier Ltd. All rights reserved.
• Rhodium-Catalyzed Asymmetric Arylation of β,γ-Unsaturated α-Ketoamides for the Construction of Nonracemic γ,γ-Diarylcarbonyl Compounds
  作者：Juanjuan Wang、Min Wang、Peng Cao、Liyin Jiang、Guihua Chen、Jian Liao

  DOI：10.1002/anie.201403325

  日期：2014.6.23

  A highly regio‐ and enantioselective rhodium‐catalyzed 1,4‐addition of arylboronic acids to β,γ‐unsaturated α‐ketoamides using a simple new chiral sulfinylphosphine ligand is described. This transformation provides an attractive approach to construct chiral nonracemic γ,γ‐diarylsubstituted carbonyl compounds, as exemplified in the concise syntheses of sertraline and tetrahydroquinoline‐2‐carboxylamide

  本文描述了使用简单的新手性亚磺酰基膦配体将高区域和对映体选择性的铑催化的1,4-芳基硼酸加成到β，γ-不饱和α-酮酰胺上的方法。这种转化为构建手性非外消旋的γ，γ-二芳基取代的羰基化合物提供了一种有吸引力的方法，如舍曲林和四氢喹啉-2-羧酰胺的简明合成中所举例说明的那样。
• Iridium/f-Amphox-Catalyzed Asymmetric Hydrogenation of Styrylglyoxylamides
  作者：Jialin Wen、Xumu Zhang、Simin Wang、Yuena Yu

  DOI：10.1055/s-0037-1609623

  日期：2018.10

  We report an iridium-catalyzed asymmetric hydrogenation reaction for the preparation of chiral homophenylalanine derivatives. Catalyzed by an iridium/f-amphox complex, the asymmetric hydrogenation of styrylglyoxylamides was conducted smoothly with turnover numbers of up to 10,000 and up to 98% ee. This method was successfully applied in a synthesis of a fragment of benazepril, a drug used for the treatment

  我们报告了用于制备手性高苯丙氨酸衍生物的铱催化不对称氢化反应。在铱/f-amphox 络合物的催化下，苯乙烯基乙醛酰胺的不对称氢化顺利进行，转化率高达 10,000，ee 高达 98%。该方法已成功应用于苯那普利片段的合成，这是一种用于治疗高血压的药物。