Phenyl-[2,2,2-trifluoro-1-(3-methoxy-phenyl)-eth-(E)-ylidene]-amine | 293743-62-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: Phenyl-[2,2,2-trifluoro-1-(3-methoxy-phenyl)-eth-(E)-ylidene]-amine
• 英文别名: 2,2,2-trifluoro-1-(3-methoxyphenyl)-N-phenylethanimine
• CAS: 293743-62-1
• 化学式: C₁₅H₁₂F₃NO
• 分子量: 279.262
• InChiKey: XLXPUESJPYQRKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  21.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Phenyl-[2,2,2-trifluoro-1-(3-methoxy-phenyl)-eth-(E)-ylidene]-amine 在 lithium aluminium tetrahydride 、 potassium carbonate 作用下， 以 乙醚 、 邻二氯苯 为溶剂， 反应 18.0h， 生成 N-(phenyl)-N-[1,1,1-trifluoro-2-(3-methoxy)-phenethyl]-4-methoxybenzamide
  参考文献：
  名称：

  Acyclic amides as estrogen receptor ligands: Synthesis, binding, activity and receptor interaction

  摘要：

  We have prepared a series of bisphenolic amides that mimic bibenzyl and homobibenzyl motifs commonly found as substructures in ligands for the estrogen receptor (ER). Representative members were prepared from three classes: N-phenyl benzamides, N-phenyl acetamides, and N-benzyl benzamides; in some cases the corresponding thiocarboxamides and sulfonamides were also prepared. Of these three classes, the N-phenyl benzamides had the highest affinity for ER, the N-phenyl acetamides had lower, and the N-benzyl benzamides were prone to fragmentation via a quinone methide intermediate. In the N-phenyl benzamide series, the highest affinity analogues had bulky N-substituents; a CF3 group, in particular, conferred high affinity. The thiocarboxamides bound better than the corresponding carboxamides and these bound better than the corresponding sulfonamides. Binding affinity comparisons suggest that the p-hydroxy group on the benzoate ring, which contributes most to the binding, is playing the role of the phenolic hydroxyl of estradiol. Computational studies and NMR and X-ray crystallographic analysis indicate that the two anilide systems studied have a strong preference for the s-cis or exo amide conformation, which places the two aromatic rings in a syn orientation. We used this structural template. together with the X-ray structure of the ER ligand binding domain, to elaborate an additional hydrogen bonding site on a benzamide system that elevated receptor binding further. When assayed on the individual ER subtypes, ER alpha and ER beta, these compounds show modest binding affinity preference for ER alpha. In a reporter gene transfection assay of transcriptional activity, the amides generally have full to nearly full agonist character on ERa, but have moderate to full antagonist character on ER beta. One high affinity carboxamide is 500-fold more potent as an agonist on ER alpha than on ER beta. This work illustrates that ER ligands having simple amide core structures can be readily prepared, but that high affinity binding requires an appropriate distribution of bulk, polarity, and functionality. The strong conformational preference of the core anilide function in all of these ligands defines a rather rigid geometry for further structural and functional expansion of these series. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00075-4
• 作为产物：
  描述：

  叠氮苯 以 乙醚 、 苯 为溶剂， 反应 2.0h， 生成 Phenyl-[2,2,2-trifluoro-1-(3-methoxy-phenyl)-eth-(E)-ylidene]-amine
  参考文献：
  名称：

  Acyclic amides as estrogen receptor ligands: Synthesis, binding, activity and receptor interaction

  摘要：

  We have prepared a series of bisphenolic amides that mimic bibenzyl and homobibenzyl motifs commonly found as substructures in ligands for the estrogen receptor (ER). Representative members were prepared from three classes: N-phenyl benzamides, N-phenyl acetamides, and N-benzyl benzamides; in some cases the corresponding thiocarboxamides and sulfonamides were also prepared. Of these three classes, the N-phenyl benzamides had the highest affinity for ER, the N-phenyl acetamides had lower, and the N-benzyl benzamides were prone to fragmentation via a quinone methide intermediate. In the N-phenyl benzamide series, the highest affinity analogues had bulky N-substituents; a CF3 group, in particular, conferred high affinity. The thiocarboxamides bound better than the corresponding carboxamides and these bound better than the corresponding sulfonamides. Binding affinity comparisons suggest that the p-hydroxy group on the benzoate ring, which contributes most to the binding, is playing the role of the phenolic hydroxyl of estradiol. Computational studies and NMR and X-ray crystallographic analysis indicate that the two anilide systems studied have a strong preference for the s-cis or exo amide conformation, which places the two aromatic rings in a syn orientation. We used this structural template. together with the X-ray structure of the ER ligand binding domain, to elaborate an additional hydrogen bonding site on a benzamide system that elevated receptor binding further. When assayed on the individual ER subtypes, ER alpha and ER beta, these compounds show modest binding affinity preference for ER alpha. In a reporter gene transfection assay of transcriptional activity, the amides generally have full to nearly full agonist character on ERa, but have moderate to full antagonist character on ER beta. One high affinity carboxamide is 500-fold more potent as an agonist on ER alpha than on ER beta. This work illustrates that ER ligands having simple amide core structures can be readily prepared, but that high affinity binding requires an appropriate distribution of bulk, polarity, and functionality. The strong conformational preference of the core anilide function in all of these ligands defines a rather rigid geometry for further structural and functional expansion of these series. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00075-4

文献信息

• Synthesis of β-CF₃ β-Amino Esters with an Indane Backbone by Rhenium-Catalyzed [3+2] Annulation
  作者：Tingjun Hu、Yuanqing Xu、Saisai Zhang、Heng-Ying Xiong、Guangwu Zhang

  DOI：10.1021/acs.orglett.0c03239

  日期：2020.11.20

  The [3+2] annulation of trifluoromethylated ketimines with acrylates has been enabled by rhenium-catalyzed C–H activation, delivering a variety of β-CF3 β-amino esters. The reaction has exhibited broad substrate generality regarding aromatic CF3-ketimines and acrylates, the ability for gram scale synthesis, and facile derivation of the annulation products. The transformation is one of the few examples

  三氟甲基化的酮亚胺与丙烯酸酯的[3 + 2]环已由铼催化C-H活化启用，提供各种β-CF的3 β氨基酯。该反应在芳族CF 3-酮亚胺和丙烯酸酯，克规模合成的能力以及环合产物的容易衍生方面表现出广泛的底物通用性。该转化是CF 3-酮亚胺的具有挑战性的sp 2 C–H键已被官能化的少数例子之一。通过这种策略快速组装具有生物学意义的重要氟化β-氨基酯将有益于相关研究，并启发了一种新的氟化基序合成方法。
• Merging Imidazolidines with a Trifluoromethylated Tetrasubstituted Carbon through Tungsten Catalyzed 1,3-Dipolar Cycloaddition
  作者：Zhifang Chen、Yufeng Zhou、Tingjun Hu、Heng-Ying Xiong、Guangwu Zhang

  DOI：10.1021/acs.joc.1c00676

  日期：2021.6.4

  acyclic CF3-ketimines have been engaged in 1,3-cycloaddition reactions. The capability for gram-scale synthesis and variant derivatizations of cycloaddition adducts illustrates the synthetic potential of this approach. This protocol provides a facile access to a rapidly enlarging pool of motifs with a trifluoromethylated fully substituted carbon.

  钨催化允许无环 CF 3 -酮亚胺和N -苄基偶氮甲碱叶立德之间发生前所未有的 1,3-偶极环加成反应，提供了一系列带有三氟甲基化四取代碳中心的新型咪唑烷。该反应似乎是挑战无环 CF 3 -酮亚胺参与 1,3-环加成反应的罕见例子之一。环加成加合物的克级合成和变体衍生的能力说明了这种方法的合成潜力。该协议提供了对具有三氟甲基化完全取代碳的快速扩大的基序池的轻松访问。