3-bromo-N-methyl-N-phenylpropanamide | 1225744-16-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-bromo-N-methyl-N-phenylpropanamide
• 英文别名: 3-Bromo-N-methyl-N-phenylpropanamide
• CAS: 1225744-16-0
• 化学式: C₁₀H₁₂BrNO
• 分子量: 242.115
• InChiKey: NUCBHVZZAYLCPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-bromo-N-methyl-N-phenylpropanamide 、 6-乙氧基-2,2,4-三甲基-1,2-二氢喹啉 在 碳酸氢钠 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以82%的产率得到3-[(2R,6R,11R)-8-hydroxy-6,11-dimethyl-1,4,5,6-tetrahydro-2,6-methano-3-benzazocin-3(2H)-yl]-N-methyl-N-phenylpropanamide
  参考文献：
  名称：

  Evaluation of N-substitution in 6,7-benzomorphan compounds

  摘要：

  6,7-Benzomorphan derivatives, exhibiting different mu, delta, and kappa receptor selectivity profiles depending on the N-substituent, represent a useful skeleton for the synthesis of new and better analgesic agents. In this work, an aromatic ring and/or alkyl residues have been used with an N-propanamide or N-acetamide spacer for the synthesis of a new series of 5,9-dimethyl-2'-hydroxy-6,7-benzomorphan derivatives (12-22). Data obtained by competition binding assays showed that the mu opioid receptor seems to prefer an interaction with the 6,7-benzomorphan ligands having an N-substituent with a propanamide spacer and less hindered amide. Highly stringent features are required for delta receptor interaction, while an N-acetamide spacer and/or bulkier amide could preferentially lead to kappa receptor selectivity. In the propanamide series, compound 12 (named LP1) displayed high mu affinity (K(i) = 0.83 nM), good delta affinity (K(i) = 29 nM) and low affinity for the kappa receptor (K(i) = 110 nM), with a selectivity ratio delta/mu and kappa/mu of 35.1 and 132.5, respectively. Further, in the adenylyl cyclase assay, LP1 displayed a mu/delta agonist profile, with IC(50) values of 4.8 and 12 nM at the mu and delta receptors, respectively. The antinociceptive potency of LP1 in the tail-flick test after sc administration in rat was comparable with the potency of morphine (ED(50) = 2.03 and 2.7 mg/kg, respectively), and was totally reversed by naloxone. LP1, possessing a mu/delta agonist profile, could represent a lead in further developing benzomorphan-based ligands with potent in vivo analgesic activity and a reduced tendency to induce side effects. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.005
• 作为产物：
  描述：

  N-甲基-N-苯基丙烯酰胺 在 三(三甲基硅基)硅烷 、 1,2-二溴乙烷 作用下， 以 乙酸乙酯 为溶剂， 反应 18.0h， 以65%的产率得到3-bromo-N-methyl-N-phenylpropanamide
  参考文献：
  名称：

  光诱导卤原子转移：卤化物自由基选择性卤化氢反应的生成

  摘要：

  描述了第一个能够通过卤素原子转移 (XAT) 产生卤化物自由基的光介导过程。这种新颖的反应模式依赖于使用 1,2-二卤乙烷通过 XAT 生成不稳定的碳自由基，XAT 在 β 断裂后释放卤化物自由基，这些卤化物自由基已用于不饱和烃的选择性卤化氢。

  DOI：

  10.1002/chem.202201495

文献信息

• Bench-Stable Stock Solutions of Silicon Grignard Reagents: Application to Iron- and Cobalt-Catalyzed Radical C(sp³ )-Si Cross-Coupling Reactions
  作者：Weichao Xue、Ryosuke Shishido、Martin Oestreich

  DOI：10.1002/anie.201807640

  日期：2018.9.10

  the preparation of silicon‐based magnesium reagents is reported. The MgBr2 used in the lithium‐to‐magnesium transmetalation step is generated in situ from 1,2‐dibromoethane and elemental magnesium in hot THF. No precipitation of MgBr2 occurs in the heat, and transmetalation at elevated temperature leads to homogeneous stock solutions of the silicon Grignard reagents that are stable and storable in the

  据报道，一种可靠的制备硅基镁试剂的方法。锂到镁的过渡金属化步骤中使用的MgBr 2是由1,2-二溴乙烷和元素镁在热THF中原位生成的。加热过程中不会发生MgBr 2的沉淀，并且在高温下的金属转移会导致硅格氏试剂的均质储备溶液，该溶液在冰箱中稳定且可储存。该方法避免了制备硅原核试剂，例如Si-Si和Si-B试剂。新的格氏试剂被用于前所未有的铁和钴催化的未活化烷基溴的交叉偶联反应。这些镁试剂的官能团耐受性极佳。
• Design, synthesis and structure–activity relationships of novel benzoxazolone derivatives as 18kDa translocator protein (TSPO) ligands
  作者：Takayuki Fukaya、Toru Kodo、Takeo Ishiyama、Hiroyoshi Kakuyama、Hiroyuki Nishikawa、Satoko Baba、Shuji Masumoto

  DOI：10.1016/j.bmc.2012.07.023

  日期：2012.9

  Selective 18 kDa translocator protein (TSPO) ligands are expected to be therapeutic agents with a wide spectrum of action on psychiatric disorders and fewer side effects. We designed novel benzoxazolone derivatives and examined the structure–activity relationship (SAR) of a series of compounds with various substituents at the amide part and C-5 position. Although a number of the synthesized compounds

  选择性的18 kDa转运蛋白（TSPO）配体有望成为对精神疾病具有广泛作用且副作用较少的治疗剂。我们设计了新颖的苯并恶唑酮衍生物，并研究了在酰胺部分和C-5位置具有多个取代基的一系列化合物的结构-活性关系（SAR）。尽管许多合成的化合物显示出高的TSPO结合亲和力，但这些化合物的药物样性质较差。这些化合物的药代动力学特性的进一步优化导致发现化合物74，该化合物在大鼠Vogel冲突模型中表现出抗焦虑作用。
• Evaluation of N-substitution in 6,7-benzomorphan compounds
  作者：Lorella Pasquinucci、Orazio Prezzavento、Agostino Marrazzo、Emanuele Amata、Simone Ronsisvalle、Zafiroula Georgoussi、Danai-Dionysia Fourla、Giovanna M. Scoto、Carmela Parenti、Giuseppina Aricò、Giuseppe Ronsisvalle

  DOI：10.1016/j.bmc.2010.06.005

  日期：2010.7

  6,7-Benzomorphan derivatives, exhibiting different mu, delta, and kappa receptor selectivity profiles depending on the N-substituent, represent a useful skeleton for the synthesis of new and better analgesic agents. In this work, an aromatic ring and/or alkyl residues have been used with an N-propanamide or N-acetamide spacer for the synthesis of a new series of 5,9-dimethyl-2'-hydroxy-6,7-benzomorphan derivatives (12-22). Data obtained by competition binding assays showed that the mu opioid receptor seems to prefer an interaction with the 6,7-benzomorphan ligands having an N-substituent with a propanamide spacer and less hindered amide. Highly stringent features are required for delta receptor interaction, while an N-acetamide spacer and/or bulkier amide could preferentially lead to kappa receptor selectivity. In the propanamide series, compound 12 (named LP1) displayed high mu affinity (K(i) = 0.83 nM), good delta affinity (K(i) = 29 nM) and low affinity for the kappa receptor (K(i) = 110 nM), with a selectivity ratio delta/mu and kappa/mu of 35.1 and 132.5, respectively. Further, in the adenylyl cyclase assay, LP1 displayed a mu/delta agonist profile, with IC(50) values of 4.8 and 12 nM at the mu and delta receptors, respectively. The antinociceptive potency of LP1 in the tail-flick test after sc administration in rat was comparable with the potency of morphine (ED(50) = 2.03 and 2.7 mg/kg, respectively), and was totally reversed by naloxone. LP1, possessing a mu/delta agonist profile, could represent a lead in further developing benzomorphan-based ligands with potent in vivo analgesic activity and a reduced tendency to induce side effects. (C) 2010 Elsevier Ltd. All rights reserved.
• Photo‐Induced Halogen‐Atom Transfer: Generation of Halide Radicals for Selective Hydrohalogenation Reactions
  作者：Lilian Geniller、Marc Taillefer、Florian Jaroschik、Alexis Prieto

  DOI：10.1002/chem.202201495

  日期：2022.8

  The first photo-mediated process enabling the generation of halide radicals by halogen-atom transfer (XAT) is described. This novel reactivity pattern relies on the use of 1,2-dihaloethanes for the generation of unstable carbon radicals by XAT, which after β-scission, release halide radicals that have been used in selective hydrohalogenations of unsaturated hydrocarbons.

  描述了第一个能够通过卤素原子转移 (XAT) 产生卤化物自由基的光介导过程。这种新颖的反应模式依赖于使用 1,2-二卤乙烷通过 XAT 生成不稳定的碳自由基，XAT 在 β 断裂后释放卤化物自由基，这些卤化物自由基已用于不饱和烃的选择性卤化氢。