1-(2-溴乙氧基)-2-(叔丁基)苯 | 1019374-12-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(2-溴乙氧基)-2-(叔丁基)苯
• 英文名称: 1-(2-bromoethoxy)-2-tert-butylbenzene
• CAS: 1019374-12-9
• 化学式: C₁₂H₁₇BrO
• 分子量: 257.17
• InChiKey: CHWACSCPLIMTIU-UHFFFAOYSA-N

物化性质

• 沸点：
  306.1±35.0 °C(Predicted)
• 密度：
  1.225±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(2-溴乙氧基)-2-(叔丁基)苯 在 potassium carbonate 、 三乙胺 、 三氟乙酸 、 potassium iodide 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 50.0h， 生成 N-(1-{[2-(t-butyl)phenoxy]ethyl}piperidin-4-yl)-N-methyl-benzenesulfonamide
  参考文献：
  名称：

  N-Alkylated arylsulfonamides of (aryloxy)ethyl piperidines: 5-HT7 receptor selectivity versus multireceptor profile

  摘要：

  The N-alkylation of the sulfonamide moiety, in a group of arylsulfonamide derivatives of (aryloxy)ethyl piperidines, may be considered as a strategy for the design of selective 5-HT7 receptor ligands or multifunctional agents to extend a polypharmacological approach to the treatment of complex diseases. The study allowed for the identification of 31 (1-methyl-N-{1-[2-(2-(t-butyl)phenoxy)ethyl]piperidin-4-yl}-N- cyclopropylmethyl-1H-pyrazole-4-sulfonamide), a potent and selective 5-HT7 receptor antagonist and 33 (1-methyl-N-{1-[2-(biphenyl-2-yloxy)ethyl] piperidin-4-yl}-N-cyclopropylmethyl-1H-pyrazole-4-sulfonamide), as multimodal 5-HT/dopamine receptor ligand, as 5-HT2A/5-HT7/D2 receptor antagonists. Both selected compounds were evaluated in vivo in a forced swim test (FST) in mice and in a novel object recognition (NOR) task in rats, demonstrating distinct antidepressant-like and pro-cognitive properties (MED = 1.25 mg/kg and 1 mg/kg, ip, respectively). These findings warrant further studies to explore the therapeutic potential of N-alkylated arylsulfonamides for the treatment of CNS disorders. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.11.041
• 作为产物：
  描述：

  2-叔丁基苯酚 、 1,2-二溴乙烷 在 potassium carbonate 、 potassium iodide 作用下， 以 丙酮 为溶剂， 以62%的产率得到1-(2-溴乙氧基)-2-(叔丁基)苯
  参考文献：
  名称：

  The multiobjective based design, synthesis and evaluation of the arylsulfonamide/amide derivatives of aryloxyethyl- and arylthioethyl- piperidines and pyrrolidines as a novel class of potent 5-HT7 receptor antagonists

  摘要：

  An analysis of the virtual combinatorial library was used for refining a pilot set of 34 derivatives and designing a targeted 38-member library of the arylamide and arylsulfonamide derivatives of aryloxyethyl- and arylthioethyl-piperidines and pyrrolidines. All compounds 24-95 were synthesized according to an elaborated parallel solid-phase method and were biologically evaluated for their affinity for 5-HT7R. Additionally, the targeted library members were tested for 5-HT1A, 5-HT6, and D-2 receptors. Selected compounds of particular interest were examined for their intrinsic activity at 5-HT7R in vitro employing a cAMP assay. The study allowed us to identify compound 68 (4-fluoro-N-(1-{2-[(propan-2-yl)phenoxylethyl}piperidin-4-yl) benzenesulfonamide) as a potent 5-HT7R ligand (K-i = 0.3 nM) with strong antagonistic properties (K-b = 1 nM) and a 1450-fold selectivity over 5-HT(1A)Rs. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.07.043

文献信息

• Palladium-Catalyzed <i>meta</i>-C–H Allylation of Arenes: A Unique Combination of a Pyrimidine-Based Template and Hexafluoroisopropanol
  作者：Sukdev Bag、Surya K、Arup Mondal、Ramasamy Jayarajan、Uttam Dutta、Sandip Porey、Raghavan B. Sunoj、Debabrata Maiti

  DOI：10.1021/jacs.0c05223

  日期：2020.7.15

  phenethyl ether, phenol, benzylsulfonyl ester, phenethylsulfonyl ester, phenylacetic acid, hydrocinnamic acid and 2-phenylbenzoic acid derivatives have been demonstrated. Interestingly, conformation-ally flexible arenes have also been selectively allylated at meta-position using allyl phosphate. A combination of 1H NMR, 31P NMR, ESI-MS, kinetic experiments, and density functional theory (DFT) computations

  控制远程选择性并在芳烃的远端位置提供新功能是当代有机合成中的一项重要努力。在这方面，模板工程和对新功能化策略的机械理解对于扩大此类方法的范围至关重要。在此，在钯催化剂、嘧啶类助剂和磷酸烯丙酯的帮助下，实现了芳烃的间位CH烯丙基化。发现 1,1,1,3,3,3-六氟异丙醇 (HFIP) 是该转化过程中的关键溶剂。已经系统地研究了 HFIP 在整个催化循环中的作用。苯乙醚、苯酚、苄基磺酰基酯、苯乙基磺酰基酯、苯乙酸、氢化肉桂酸和 2-苯基苯甲酸衍生物的广泛底物范围已被证明。有趣的是，构象灵活的芳烃也已使用磷酸烯丙酯在间位选择性地烯丙基化。1H NMR、31P NMR、ESI-MS、动力学实验和密度泛函理论 (DFT) 计算的组合表明，反应通过配体辅助的间位 CH 活化进行，烯丙基加成形成 Pd-π-烯丙基复合物然后是翻转确定 CC 键形成步骤，导致间位烯丙基化产物。
• Amino Acid Hot Spots of Halogen Bonding: A Combined Theoretical and Experimental Case Study of the 5-HT₇ Receptor
  作者：Rafał Kurczab、Vittorio Canale、Grzegorz Satała、Paweł Zajdel、Andrzej J. Bojarski

  DOI：10.1021/acs.jmedchem.8b00828

  日期：2018.10.11

  A computational approach combining a structure-activity relationship library of halogenated and the corresponding unsubstituted ligands (called XSAR) with QM-based molecular docking and binding free energy calculations was used to search for amino acids frequently targeted by halogen bonding (hot spots) in a 5-HT7R as a case study. The procedure identified two sets of hot spots, extracellular (D2.65, T2.64, and E7.35) and transmembrane (C3.36, TS.39, and S5.42), which were further verified by a synthesized library of halogenated arylsulfonamide derivatives of (aryloxy)ethylpiperidines. It was found that a halogen bond formed between T5.39 and a bromine atom at 3-position of the aryloxy fragment caused the most remarkable, 35-fold increase in binding affinity for 5-HT7R when compared to the nonhalogenated analog. The proposed paradigm of halogen bonding hot spots was additionally verified on D-4 dopamine receptor showing that it can be used in rational drug design/optimization for any protein target.
• Towards new 5-HT 7 antagonists among arylsulfonamide derivatives of (aryloxy)ethyl-alkyl amines: Multiobjective based design, synthesis, and antidepressant and anxiolytic properties
  作者：Vittorio Canale、Rafał Kurczab、Anna Partyka、Grzegorz Satała、Tomasz Lenda、Magdalena Jastrzębska-Więsek、Anna Wesołowska、Andrzej J. Bojarski、Paweł Zajdel

  DOI：10.1016/j.ejmech.2015.11.040

  日期：2016.1

  A series of 39 arylsulfonamide/amide derivatives of (aryloxy)ethyl alkyl amines, was designed with the support of the Virtual Combinatorial Library-Virtual Screening protocol, and synthesized using solid-phase methodologies. Representative compounds were biologically evaluated for their affinity for 5-HT(7)Rs and for their selectivity over related 5-HTRs (5-HT(1A)Rs, 5-HT(2A)Rs, 5-HT(6)Rs), dopamine D(2)Rs and adrenergic alpha(1)Rs. The study identified the derivatives 27 (3-fluoro-N-1-[2-(2-cyclopenrylphenoxy) ethyl]piperidin-4-yl}-benzenesulfonamide; PZ-1417) and 35 (4-fluoro-N-(1-2-[(propan-2-yl)phenoxy] ethyl}-8-azabicyclo[3.2.1]octan-3-yl)-benzenesulfonamide; PZ-1150) as being potent 5-HT7R antagonists with antidepressant and anxiolytic properties in the forced swim test (0.625-5 mg/kg and 0.625 mg/kg, respectively), the tail suspension test (0.625 mg/kg and 0.625 mg/kg, respectively), and in four plate test (0.625 mg/kg and 1.25-2.5 mg/kg, respectively) in mice. It has to be stressed that new compounds displayed higher activity than that of SB-269970, a reference 5-HT7R antagonist. Finally, the study provided valuable insight into the development of potential therapeutic agents for the treatment of CNS disorders. (C) 2015 Elsevier Masson SAS. All rights reserved.