(S)-1-(4-bromophenyl)-5-((tert-butyldimethylsilyloxy)methyl)pyrrolidin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (S)-1-(4-bromophenyl)-5-((tert-butyldimethylsilyloxy)methyl)pyrrolidin-2-one
• 英文别名: (5S)-1-(4-bromophenyl)-5-tert-butyldimethylsilyloxymethyl-2-pyrrolidinone；(5S)-1-(4-bromophenyl)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]pyrrolidin-2-one
• 化学式: C₁₇H₂₆BrNO₂Si
• 分子量: 384.388
• InChiKey: MNMNXXZHDOMIBU-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.97
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-1-(4-bromophenyl)-5-((tert-butyldimethylsilyloxy)methyl)pyrrolidin-2-one 在 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 四丁基氟化铵 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 N,N-二甲基甲酰胺 、 三氟乙酸 为溶剂， -78.0~100.0 ℃ 、344.75 kPa 条件下， 反应 162.0h， 生成 ((2S,5S)-5-methyl-1-(4-(2-methylbenzyl)phenyl)pyrrolidin-2-yl)methanol
  参考文献：
  名称：

  Discovery of Pyrrolidine-Containing GPR40 Agonists: Stereochemistry Effects a Change in Binding Mode

  摘要：

  A novel series of pyrrolidine-containing GPR40 agonists is described as a potential treatment for type 2 diabetes. The initial pyrrolidine hit was modified by moving the position of the carboxylic acid, a key pharmacophore for GPR40. Addition of a 4-cis-CF3 to the pyrrolidine improves the human GPR40 binding K-i and agonist efficacy. After further optimization, the discovery of a minor enantiomeric impurity with agonist activity led to the finding that enantiomers (R,R)-68 and (S,S)-68 have differential effects on the radioligand used for the binding assay, with (R,R)-68 potentiating the radioligand and (S,S)-68 displacing the radioligand. Compound (R,R)-68 activates both G(q)-coupled intracellular Ca2+ flux and G(s)-coupled cAMP accumulation. This signaling bias results in a dual mechanism of action for compound (R,R)-68, demonstrating glucose-dependent insulin and GLP-1 secretion in vitro. In vivo, compound (R,R)-68 significantly lowers plasma glucose levels in mice during an oral glucose challenge, encouraging further development of the series.

  DOI：

  10.1021/acs.jmedchem.6b01559
• 作为产物：
  描述：

  1,4-二溴苯 、 (S)-5-(((叔丁基二甲基甲硅烷基)氧基)甲基)吡咯烷-2-酮 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 以62%的产率得到(S)-1-(4-bromophenyl)-5-((tert-butyldimethylsilyloxy)methyl)pyrrolidin-2-one
  参考文献：
  名称：

  Synthesis of chiral N -aryl pyrrolidinones via a palladium-catalyzed cross-coupling reaction

  摘要：

  The direct synthesis of non-racemic N-aryl pyrrolidinones through the application of the Buchwald/Hartwig aryl amination reaction is reported. These reactions proceed in generally good yield, with a variety of electron deficient aryl bromides and with retention of stereochemical purity. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(01)01501-5

文献信息

• Palladium-catalyzed aryl-amidation. Synthesis of non-racemic N-aryl lactams
  作者：R.Greg Browning、Vivek Badarinarayana、Hossen Mahmud、Carl J Lovely

  DOI：10.1016/j.tet.2003.11.008

  日期：2004.1

  The Buchwald/Hartwig aryl amination method was used to construct a series of chiral, non-racemic N-aryl pyrrolidinones from a common pyrrolidinone precursor and the corresponding aryl bromide. The stereochemical integrity of the N-aryl lactam after cross-coupling was proven by synthesis of the racemic compounds and comparison by H-1 NMR spectroscopy using Pirkle's chiral solvating agent. (C) 2003 Elsevier Ltd. All rights reserved.