(+/-)-1-benzyl-4-bromomethylpyrrolidin-2-one | 1227725-28-1

• 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: (+/-)-1-benzyl-4-bromomethylpyrrolidin-2-one
• 英文别名: 1-benzyl-4-(bromomethyl)pyrrolidin-2-one
• CAS: 1227725-28-1
• 化学式: C₁₂H₁₄BrNO
• 分子量: 268.153
• InChiKey: QUVGINIVEUZNKH-UHFFFAOYSA-N

物化性质

• 沸点：
  414.3±28.0 °C(Predicted)
• 密度：
  1.420±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 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：

  (+/-)-1-benzyl-4-bromomethylpyrrolidin-2-one 在 吡啶 、 正丁基锂 、 双氧水 、 sodium ethanolate 、 二异丙胺 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 1-benzyl-3-[(3,5-dichlorophenoxy)methyl]-2H-pyrrol-5-one
  参考文献：
  名称：

  Substituted pyrazolones require N2 hydrogen bond donating ability to protect against cytotoxicity from protein aggregation of mutant superoxide dismutase 1

  摘要：

  Amyotrophic lateral sclerosis (ALS) is a debilitating and fatal neurodegenerative disease. Although the cause remains unknown, misfolded protein aggregates are seen in neurons of sporadic ALS patients, and familial ALS mutations, including mutations in superoxide dismutase 1 (SOD1), produce proteins with an increased propensity to misfold and aggregate. A structure activity relationship of a lead scaffold exhibiting neuroprotective activity in a G93A-SOD1 mouse model for ALS has been further investigated in a model PC12 cellular assay. Synthesis of biotinylated probes at the N-1 nitrogen of the pyrazolone ring gave compounds (5d-e) that retained activity within 10-fold of the proton-bearing lead compound (5a) and were equipotent with a sterically less cumbersome N-1-methyl substituted analogue (5b). However, when methyl substitution was introduced at N-1 and N-2 of the pyrazolone ring, the compound was inactive (5c). These data led us to investigate further the pharmacophoric nature of the pyrazolone unit. A range of N-1 substitutions were tolerated, leading to the identification of an N-1-benzyl substituted pyrazolone (5m), equipotent with 5a. Substitution at N-2 or excision of N-2, however, removed all activity. Therefore, the hydrogen bond donating ability of the N-2-H of the pyrazolone ring appears to be a critical part of the structure, which will influence further analogue synthesis. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.114
• 作为产物：
  描述：

  1-苄基-4-甲醇-2-吡咯烷酮 在 三溴化磷 作用下， 以 甲苯 为溶剂， 以64%的产率得到(+/-)-1-benzyl-4-bromomethylpyrrolidin-2-one
  参考文献：
  名称：

  2-吡啶酮中的分子内1,6-加成。机制和综合范围。

  摘要：

  探究了在2-吡啶酮部分中烯醇化物的分子内1，6-加成的范围和局限性，该反应已发现在羽扇豆生物碱的合成中得到应用。已经证明这种亲核加成过程是可逆的，并且在（稳定性较差的）酰胺和内酰胺烯酸酯（易于形成五元和六元双/三环产物）的情况下受到青睐。已评估了备选的烯醇化物（酮，酯，硫代内酰胺）和各种不同的受体（异喹啉酮，嘧啶酮，吡嗪酮，吡啶并吡嗪酮），并使用包括原位红外在内的多种技术鉴定和表征了一系列竞争性副反应。

  DOI：

  10.1021/jo100514a

文献信息

• Intramolecular 1,6-Addition to 2-Pyridones. Mechanism and Synthetic Scope.
  作者：Timothy Gallagher、Ian Derrick、Patrick M. Durkin、Claire A. Haseler、Christoph Hirschhäuser、Pietro Magrone

  DOI：10.1021/jo100514a

  日期：2010.6.4

  2-pyridone moiety, a reaction that has found application in the synthesis of the lupin alkaloids, have been probed. This nucleophilic addition process has been shown to be reversible and favored in the case of (less stabilized) amide and lactam enolates, which readily form five- and six-membered bi-/tricyclic products. Alternative enolates (ketone, ester, thiolactam) and a variety of different acceptors (isoquinolinone

  探究了在2-吡啶酮部分中烯醇化物的分子内1，6-加成的范围和局限性，该反应已发现在羽扇豆生物碱的合成中得到应用。已经证明这种亲核加成过程是可逆的，并且在（稳定性较差的）酰胺和内酰胺烯酸酯（易于形成五元和六元双/三环产物）的情况下受到青睐。已评估了备选的烯醇化物（酮，酯，硫代内酰胺）和各种不同的受体（异喹啉酮，嘧啶酮，吡嗪酮，吡啶并吡嗪酮），并使用包括原位红外在内的多种技术鉴定和表征了一系列竞争性副反应。
• Lactam Enolate-Pyridone Addition: Synthesis of 4-Halocytisines
  作者：Timothy Gallagher、Patrick Durkin、Pietro Magrone、Stella Matthews、Clelia Dallanoce

  DOI：10.1055/s-0030-1259006

  日期：2010.11

  The application of a lactam enolate-pyridone addition sequence, originally developed for cytisine, has been applied successfully to generate the first examples of 4-halocytisines. Variation of the lactam component provides cyfusine and 4-fluorocyfusine.

  内酰胺烯醇-吡啶酮加成序列最初是为胞嘧啶开发的，现已成功应用于生成首批 4-卤代胞嘧啶。内酰胺成分的变化提供了 cyfusine 和 4-氟 cyfusine。
• Substituted pyrazolones require N2 hydrogen bond donating ability to protect against cytotoxicity from protein aggregation of mutant superoxide dismutase 1
  作者：Paul C. Trippier、Radhia Benmohamed、Donald R. Kirsch、Richard B. Silverman

  DOI：10.1016/j.bmcl.2012.08.114

  日期：2012.11

  Amyotrophic lateral sclerosis (ALS) is a debilitating and fatal neurodegenerative disease. Although the cause remains unknown, misfolded protein aggregates are seen in neurons of sporadic ALS patients, and familial ALS mutations, including mutations in superoxide dismutase 1 (SOD1), produce proteins with an increased propensity to misfold and aggregate. A structure activity relationship of a lead scaffold exhibiting neuroprotective activity in a G93A-SOD1 mouse model for ALS has been further investigated in a model PC12 cellular assay. Synthesis of biotinylated probes at the N-1 nitrogen of the pyrazolone ring gave compounds (5d-e) that retained activity within 10-fold of the proton-bearing lead compound (5a) and were equipotent with a sterically less cumbersome N-1-methyl substituted analogue (5b). However, when methyl substitution was introduced at N-1 and N-2 of the pyrazolone ring, the compound was inactive (5c). These data led us to investigate further the pharmacophoric nature of the pyrazolone unit. A range of N-1 substitutions were tolerated, leading to the identification of an N-1-benzyl substituted pyrazolone (5m), equipotent with 5a. Substitution at N-2 or excision of N-2, however, removed all activity. Therefore, the hydrogen bond donating ability of the N-2-H of the pyrazolone ring appears to be a critical part of the structure, which will influence further analogue synthesis. (C) 2012 Elsevier Ltd. All rights reserved.