N-(1-苄基哌啶-4-基)-2-(2-溴苯基)乙酰胺 | 208184-69-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: N-(1-苄基哌啶-4-基)-2-(2-溴苯基)乙酰胺
• 英文名称: N-(1-benzylpiperidin-4-yl)-2-bromophenylacetamide
• 英文别名: N-(1-Benzylpiperidin-4-yl)-2-(2-bromophenyl)acetamide
• CAS: 208184-69-4
• 化学式: C₂₀H₂₃BrN₂O
• 分子量: 387.319
• InChiKey: HWTWCGBXKVKYFN-UHFFFAOYSA-N

物化性质

• 沸点：
  544.3±50.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(1-苄基哌啶-4-基)-2-(2-溴苯基)乙酰胺 在 palladium diacetate 、 palladium on activated charcoal ammonium formate 、 potassium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 、 苯硼酸 作用下， 以 甲醇 、 叔丁醇 为溶剂， 反应 2.05h， 生成 1,3-二氢-1-(-4-哌啶基)(2H)吲哚-2-酮
  参考文献：
  名称：

  Piperidine amides as 11β-hydroxysteroid dehydrogenase type 1 inhibitors

  摘要：

  A series of piperidine amide inhibitors of human 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) were identified via modifications of the HTS hit compound 1. The synthesis, in vitro biological evaluation, and structure-activity relationship of these compounds are presented. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.083
• 作为产物：
  描述：

  4-氨基-1-苄基哌啶 、 2-溴苯乙酰氯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 以78%的产率得到N-(1-苄基哌啶-4-基)-2-(2-溴苯基)乙酰胺
  参考文献：
  名称：

  A novel synthesis of N-(piperidin-4-yl)-1,3-dihydroindol-2-one via an intramolecular Pd-catalyzed amination

  摘要：

  A novel efficient synthetic route to the pharmaceutical key intermediate N-(piperidin-4-yl)-1,3-dihydroindol-2-one is described. The key step involves a high-yielding intramolecular palladium-catalyzed amination reaction using Buchwald's X-Phos ligand under mild reaction conditions. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2004.09.121

文献信息

• Synthesis and Quantitative Structure−Activity Relationships of <i>N</i>-(1-Benzylpiperidin-4-yl)phenylacetamides and Related Analogues as Potent and Selective σ₁ Receptor Ligands
  作者：Yunsheng Huang、Philip S. Hammond、Brian R Whirrett、Ross J. Kuhner、Li Wu、Steven R. Childers、Robert H. Mach

  DOI：10.1021/jm980032l

  日期：1998.6.1

  A series of N-(1-benzylpiperidin-4-yl)pherlylacetamide derivatives was synthesized and evaluated for affinity at or and oz receptors. Most of these compounds showed a high affinity for sigma(1) receptors and a low to moderate affinity for sigma(2) receptors. The unsubstituted compound N-(1-benzylpiperidin-4-yl)phenylacetamide, 1, displayed a high affinity and selectivity for sigma(1) receptors (K-i) values of 3.90 nM for sigma(1) receptors and 240 nM for sigma(2) receptors. The influence of substitutions on the phenylacetamide aromatic ring on binding at both the sigma(1) and sigma(2) receptor has been examined through Hansch-type quantitative structure-activity relationship (QSAR) studies. In general, all 3-substituted compounds, except for the OH group, had a higher affinity for both sigma(1) and sigma(2) receptors when compared with the corresponding 2- and 4-substituted analogues. The selectivity for sigma(1) receptors displayed a trend of 3 > 2 approximate to 4 for Cl, Pr, F, NO2, and OMe substituted analogues. Halogen substitution on the aromatic ring generally increased the affinity for sigma(2) receptors while maintaining a similar affinity for sigma(1) receptors. Substitution with electron-donating groups, such as OH, OMe, or NH2, resulted in weak or negligible affinity for sigma(2) receptors and a moderate affinity for sigma(1) receptors. The 2-fluoro-substituted analogue, 11, exhibited the highest selectivity for sigma(1) receptors among all compounds tested, with a K-i value of 3.56 nM for sigma(1) receptors and 667 nM for sigma(2) receptors. Compounds 1, 5, 9, 11, and 20 had no affinity for dopamine D-2 (IC50 > 10 000 nM) and D-3 (IC50 > 10 000 nM) receptors. The nanomolar binding affinity and high selectivity for sigma(1) receptors suggest that these compounds may be developed as potential radiotracers for positron emission tomography or single photon emission computerized tomography imaging studies.
• An efficient one-pot synthesis of novel 4-aryl-1-methyloxindoles
  作者：Adri van den Hoogenband、Jos H.M. Lange、Wouter I. Iwema-Bakker、Jack A.J. den Hartog、Jord van Schaik、Rolf W. Feenstra、Jan Willem Terpstra

  DOI：10.1016/j.tetlet.2006.04.103

  日期：2006.6

  An unprecedented synthetic approach to novel 4-aryl-1-methyloxindoles is described. The method involves the intramolecular palladium-catalyzed amidation of N-methyl-2,6-dibromophenylacetamide followed by an in situ Suzuki cross-coupling reaction with a (hetero)arylboronic acid in a one-pot reaction. (c) 2006 Elsevier Ltd. All rights reserved.
• A novel synthesis of N-(piperidin-4-yl)-1,3-dihydroindol-2-one via an intramolecular Pd-catalyzed amination
  作者：Adri van den Hoogenband、Jack A.J. den Hartog、Jos H.M. Lange、Jan Willem Terpstra

  DOI：10.1016/j.tetlet.2004.09.121

  日期：2004.11

  A novel efficient synthetic route to the pharmaceutical key intermediate N-(piperidin-4-yl)-1,3-dihydroindol-2-one is described. The key step involves a high-yielding intramolecular palladium-catalyzed amination reaction using Buchwald's X-Phos ligand under mild reaction conditions. (C) 2004 Elsevier Ltd. All rights reserved.
• Piperidine amides as 11β-hydroxysteroid dehydrogenase type 1 inhibitors
  作者：Katarina Flyrén、Lars O. Bergquist、Victor M. Castro、Christopher Fotsch、Lars Johansson、David J. St. Jean、Lori Sutin、Meredith Williams

  DOI：10.1016/j.bmcl.2007.03.083

  日期：2007.6

  A series of piperidine amide inhibitors of human 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) were identified via modifications of the HTS hit compound 1. The synthesis, in vitro biological evaluation, and structure-activity relationship of these compounds are presented. (c) 2007 Elsevier Ltd. All rights reserved.