2-[N-(2-phenylethyl)-N-(trifluoromethylsulfonyl)amino]aceticacid | 193689-44-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-[N-(2-phenylethyl)-N-(trifluoromethylsulfonyl)amino]aceticacid
• 英文别名: N-Phenethyl-N-[(trifluoromethyl)sulfonyl]glycine；2-[2-phenylethyl(trifluoromethylsulfonyl)amino]acetic acid
• CAS: 193689-44-0
• 化学式: C₁₁H₁₂F₃NO₄S
• 分子量: 311.282
• InChiKey: LDODHQWTKKIAKH-UHFFFAOYSA-N

物化性质

• 沸点：
  405.4±55.0 °C(Predicted)
• 密度：
  1.474±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-[N-(2-phenylethyl)-N-(trifluoromethylsulfonyl)amino]aceticacid 在 sodium tetrahydroborate 、 四磷十氧化物 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 氘代乙腈 为溶剂， 反应 25.5h， 生成 3-benzyl-2,3,4,5-tetrahydro-1H-3-benzazepin-1-ol
  参考文献：
  名称：

  Role of the phenolic OH moiety of GluN2B-selective NMDA antagonists with 3-benzazepine scaffold

  摘要：

  In order to analyze the role of the phenolic OH moiety of ifenprodil (1) and 3-benzazepin-1,7-diol 2 for the affinity and selectivity at GluN2B subunit containing NMDA receptors, the 3-benzazepin-1-ols 3 were designed, synthesized and pharmacologically evaluated and furthermore, the molecular interactions of the phenylbutyl derivative 3c with the GluN2B receptor were investigated. In order to avoid decarbonylation during the intramolecular Friedel-Crafts acylation of 11, the N-atom has to be protected with a trifluoromethylsulfonyl group. The second key step of the synthesis was the removal of the N-triflyl group, which was realized by K2CO3 induced elimination of trifluoromethanelsulfinate (F3CSO2-). In receptor binding studies with the radioligand [3H] ifenprodil the 3-benzazepin-1-ol 3c revealed a GluN2B affinity of 73 nM indicating that the phenolic OH moiety of 1 and 2 is not essential but favorable for high GluN2B affinity. In docking studies 3-benzazepin-1-ol 3c shows the same binding pose as ifenprodil-keto 1A in the X-ray crystal structure. H-bond interactions and lipophilic interactions of 3c and 1A are very similar. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.12.067
• 作为产物：
  描述：

  N-(2-苯基乙基)三氟甲磺酰胺 在 sodium hydroxide 、 sodium hydride 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 2-[N-(2-phenylethyl)-N-(trifluoromethylsulfonyl)amino]aceticacid
  参考文献：
  名称：

  Use of the Triflamide Group for Friedel-Crafts Acylation of N-(b-Phenethyl)amino Acids to 3-Benzazepine Derivatives

  摘要：

  Triflamides of N-(beta-phenethyl)amino acids (1) were treated with P2O5 under the Friedel-Crafts acylation conditions to give the 3-benzazepines in good yields. N-(beta-Phenethyl)-N-triflylvaline (If) and phenylglycine (1g) were efficiently prepared from the corresponding N-triflylamino acids and beta-phenethyl alcohol via the Mitsunobu reaction.

  DOI：

  10.3987/com-97-7803

文献信息

• [EN] MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR<br/>[FR] MODULATEURS DU RÉGULATEUR DE LA CONDUCTANCE TRANSMEMBRANAIRE DE LA MUCOVISCIDOSE
  申请人：VERTEX PHARMA

  公开号：WO2022076625A1

  公开（公告）日：2022-04-14

  This disclosure provides modulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) having core structure (I), pharmaceutical compositions containing at least one such modulator, methods of treatment of CFTR mediated diseases, including cystic fibrosis, using such modulators and pharmaceutical compositions, combination pharmaceutical compositions and combination therapies, and processes and intermediates for making such modulators.

  本发明提供了囊性纤维化跨膜传导调节因子（CFTR）的调节剂，其具有核心结构（I），包含至少一种这样的调节剂的制药组合物，使用这样的调节剂和制药组合物治疗CFTR介导的疾病，包括囊性纤维化，组合制药组合物和组合疗法，以及制造这样的调节剂的过程和中间体。
• Use of the Triflamide Group for Friedel-Crafts Acylation of N-(b-Phenethyl)amino Acids to 3-Benzazepine Derivatives
  作者：Masami Kawase、Noboru Motohashi、Masayuki Niwa、Masakatsu Nozaki

  DOI：10.3987/com-97-7803

  日期：——

  Triflamides of N-(beta-phenethyl)amino acids (1) were treated with P2O5 under the Friedel-Crafts acylation conditions to give the 3-benzazepines in good yields. N-(beta-Phenethyl)-N-triflylvaline (If) and phenylglycine (1g) were efficiently prepared from the corresponding N-triflylamino acids and beta-phenethyl alcohol via the Mitsunobu reaction.
• Role of the phenolic OH moiety of GluN2B-selective NMDA antagonists with 3-benzazepine scaffold
  作者：Sougata Dey、Dirk Schepmann、Bernhard Wünsch

  DOI：10.1016/j.bmcl.2015.12.067

  日期：2016.2

  In order to analyze the role of the phenolic OH moiety of ifenprodil (1) and 3-benzazepin-1,7-diol 2 for the affinity and selectivity at GluN2B subunit containing NMDA receptors, the 3-benzazepin-1-ols 3 were designed, synthesized and pharmacologically evaluated and furthermore, the molecular interactions of the phenylbutyl derivative 3c with the GluN2B receptor were investigated. In order to avoid decarbonylation during the intramolecular Friedel-Crafts acylation of 11, the N-atom has to be protected with a trifluoromethylsulfonyl group. The second key step of the synthesis was the removal of the N-triflyl group, which was realized by K2CO3 induced elimination of trifluoromethanelsulfinate (F3CSO2-). In receptor binding studies with the radioligand [3H] ifenprodil the 3-benzazepin-1-ol 3c revealed a GluN2B affinity of 73 nM indicating that the phenolic OH moiety of 1 and 2 is not essential but favorable for high GluN2B affinity. In docking studies 3-benzazepin-1-ol 3c shows the same binding pose as ifenprodil-keto 1A in the X-ray crystal structure. H-bond interactions and lipophilic interactions of 3c and 1A are very similar. (C) 2015 Elsevier Ltd. All rights reserved.