2-<2-(tert-butyldimethylsiloxy)ethyl>piperidine | 153108-62-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-<2-(tert-butyldimethylsiloxy)ethyl>piperidine
• 英文别名: Piperidine, 2-[2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]ethyl]-；tert-butyl-dimethyl-(2-piperidin-2-ylethoxy)silane
• CAS: 153108-62-4
• 化学式: C₁₃H₂₉NOSi
• 分子量: 243.465
• InChiKey: WDABCPAUFJREBO-UHFFFAOYSA-N

物化性质

• 沸点：
  274.3±13.0 °C(Predicted)
• 密度：
  0.865±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.54
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-<2-(tert-butyldimethylsiloxy)ethyl>piperidine 在 正丁基锂 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 正己烷 、 丙酮 、 甲苯 为溶剂， 反应 36.58h， 生成 1-(3-Bromo-prop-2-ynyl)-2-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-piperidine
  参考文献：
  名称：

  A Ring-Closing Yne-Carbonyl Metathesis of Ynamides

  摘要：

  An acid-catalyzed ring-closing ynamide-carbonyl metathesis is described here. This hetero RCM methodology is applicable to the construction of carbocycles as well as heterocycles such as chromenes, quinolizidines, indolizidines, and pyrrolizidines.

  DOI：

  10.1021/ol052487s
• 作为产物：
  描述：

  2-哌啶乙醇 在 咪唑 、 palladium on activated charcoal 、 氢气 、 sodium carbonate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 3.0h， 生成 2-<2-(tert-butyldimethylsiloxy)ethyl>piperidine
  参考文献：
  名称：

  Non-nucleoside Inhibitors of the Measles Virus RNA-Dependent RNA Polymerase: Synthesis, Structure–Activity Relationships, and Pharmacokinetics

  摘要：

  The measles virus (MeV), a member of the paramyxovirus family, is an important cause of pediatric morbidity and mortality worldwide. In an effort to provide therapeutic treatments for improved measles management, we previously identified a small, non-nucleoside organic inhibitor of the viral RNA-dependent RNA polymerase by means of high-throughput screening. Subsequent structure-activity relationship (SAR) studies around the corresponding pyrazole carboxamide scaffold led to the discovery of 2 (AS-136a), a first generation lead with low nanomolar potency against life MeV and attractive physical properties suitable for development. However, its poor water solubility and low oral bioavailability (F) in rat suggested that the lead could benefit from further SAR studies to improve the biophysical characteristics of the compound. Optimization of in vitro potency and aqueous solubility led to the discovery of 2o (ERDRP-00519), a potent inhibitor of MeV (EC50 = 60 nM) with an aqueous solubility of approximately 60 mu g/mL. The agent shows a 10-fold exposure (AUC/C-max) increase in the rat model relative to 2, displays near dose proportionality in the range of 10-50 mg/kg and exhibits good oral bioavailability (F = 39%). The significant solubility increase appears linked to the improved oral bioavailability.

  DOI：

  10.1021/jm201699w

文献信息

• Carbamoylimidazolium and thiocarbamoylimidazolium salts: novel reagents for the synthesis of ureas, thioureas, carbamates, thiocarbamates and amides
  作者：Justyna A. Grzyb、Ming Shen、Chiaki Yoshina-Ishii、W. Chi、R.Stanley Brown、Robert A. Batey

  DOI：10.1016/j.tet.2005.05.056

  日期：2005.7

  Carbamoylimidazolium salts act as efficient N,N-disubstituted carbamoylating reagents. These salts are readily prepared by the sequential treatment of secondary amines with N,N′-carbonyldiimidazole (CDI) and iodomethane. The carbamoylimidazolium salts are more efficient carbamoyl transfer reagents than the intermediate carbamoylimidazoles, as a result of the ‘imidazolium’ effect. Kinetic studies on

  氨基甲酰咪唑鎓盐可作为有效的N，N-二取代的氨基甲酰化试剂。这些盐很容易通过用N，N依次处理仲胺来制备′-羰基二咪唑（CDI）和碘甲烷。由于“咪唑鎓”效应，因此氨基甲酰咪唑鎓盐是比中间氨基甲酰咪唑更有效的氨基甲酰转移试剂。对氨基甲酰咪唑盐和氨基甲酰咪唑鎓盐的碱促进水解的动力学研究表明，其加速百倍。该盐与胺，硫醇，酚/醇和羧酸以高收率反应，而无需对产物进行后续色谱纯化，分别生产尿素，硫代氨基甲酸酯，氨基甲酸酯和酰胺。还从仲胺和N，N′-硫代羰基二咪唑（TCDI）合成类似的硫代氨基甲酰咪唑鎓盐，然后用碘代甲烷甲基化。
• Carbamoylimidazolium salts as diversification reagents: an application to the synthesis of tertiary amides from carboxylic acids
  作者：Justyna A. Grzyb、Robert A. Batey

  DOI：10.1016/j.tetlet.2003.08.026

  日期：2003.9

  preparation of tertiary amides from carbamoylimidazolium salts and carboxylic acids is described. The transformation occurs at room temperature and under relatively mild conditions. The carbamoylimidazolium salts are obtained from the reaction of secondary amines with N,N′-carbonyldiimidazole, followed by methylation with methyl iodide. The utility of this reaction was demonstrated in the formation of Weinreb

  描述了一种从氨基甲酰咪唑鎓盐和羧酸制备叔酰胺的有效方法。该转变发生在室温和相对温和的条件下。由仲胺与N，N'-羰基二咪唑反应，然后与碘甲烷甲基化，得到氨基甲酰咪唑鎓盐。在Weinreb酰胺的形成和稠合双环酰胺的短合成中证明了该反应的效用。现在，通过引入该反应，可以在单一条件下将氨基甲酰咪唑鎓盐用于叔酰胺，脲，氨基甲酸酯和硫代氨基甲酸酯的形成。
• Efficient synthesis of heterocyclic compounds using ethenetricarboxylic acid diesters
  作者：Shoko Yamazaki、Yuko Iwata、Yugo Fukushima

  DOI：10.1039/b818878e

  日期：——

  Ethenetricarboxylic acid diester 1a is a useful compound bearing two reactive sites, a CO2H group and a Michael acceptor. Reactions of 1a and reagents with oxygen and nitrogen nucleophilic moieties have been examined. The reaction of 1a with 2-aminoalcohols in the presence of EDCI and HOBt in one pot gave N,O-containing heterocyclic compounds, regioselectively. The stepwise method has also been carried

  乙三羧酸二酯1a是有用的化合物，带有两个反应位，一个CO 2 H基团和一个迈克尔受体。的反应1A和试剂与氧和氮亲核部分已被检查。在EDCI存在下1a与2-氨基醇的反应霍比特 一锅给 ñ，Ô区域选择性地含有杂环化合物。还已经执行了逐步方法。脱保护ñ -Boc 保护的氨基酯，然后进行碱性水后处理，得到各种 1,4-恶嗪衍生品。O- TBS保护的酰胺的脱保护也会导致自发环化并提供1,4-恶嗪衍生品。它们具有与一锅法反应相反的区域化学。因此，可以制备酯或酰胺的区域异构体。这些合成方法代表了构建多种杂环系统（例如吗啉衍生的杂环）的新通用策略。
• Aoyagi, Sakae; Wang, Tzu-Chueh; Kibayashi, Chihiro, Journal of the American Chemical Society, 1993, vol. 115, # 24, p. 11393 - 11409
  作者：Aoyagi, Sakae、Wang, Tzu-Chueh、Kibayashi, Chihiro

  DOI：——

  日期：——
• Non-nucleoside Inhibitors of the Measles Virus RNA-Dependent RNA Polymerase: Synthesis, Structure–Activity Relationships, and Pharmacokinetics
  作者：J. Maina Ndungu、Stefanie A. Krumm、Dan Yan、Richard F. Arrendale、G. Prabhakar Reddy、Taylor Evers、Randy Howard、Michael G. Natchus、Manohar T. Saindane、Dennis C. Liotta、Richard K. Plemper、James P. Snyder、Aiming Sun

  DOI：10.1021/jm201699w

  日期：2012.5.10

  The measles virus (MeV), a member of the paramyxovirus family, is an important cause of pediatric morbidity and mortality worldwide. In an effort to provide therapeutic treatments for improved measles management, we previously identified a small, non-nucleoside organic inhibitor of the viral RNA-dependent RNA polymerase by means of high-throughput screening. Subsequent structure-activity relationship (SAR) studies around the corresponding pyrazole carboxamide scaffold led to the discovery of 2 (AS-136a), a first generation lead with low nanomolar potency against life MeV and attractive physical properties suitable for development. However, its poor water solubility and low oral bioavailability (F) in rat suggested that the lead could benefit from further SAR studies to improve the biophysical characteristics of the compound. Optimization of in vitro potency and aqueous solubility led to the discovery of 2o (ERDRP-00519), a potent inhibitor of MeV (EC50 = 60 nM) with an aqueous solubility of approximately 60 mu g/mL. The agent shows a 10-fold exposure (AUC/C-max) increase in the rat model relative to 2, displays near dose proportionality in the range of 10-50 mg/kg and exhibits good oral bioavailability (F = 39%). The significant solubility increase appears linked to the improved oral bioavailability.