(S)-N-Boc-piperidine-2-carboxylic acid 2,6-dimethylphenyl amide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-N-Boc-piperidine-2-carboxylic acid 2,6-dimethylphenyl amide
• 英文别名: tert-butyl (2S)-2-[(2,6-dimethylphenyl)carbamoyl]piperidine-1-carboxylate
• 化学式: C₁₉H₂₈N₂O₃
• 分子量: 332.443
• InChiKey: YOJQBLCOXHTGNM-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-N-Boc-piperidine-2-carboxylic acid 2,6-dimethylphenyl amide 在 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 14.25h， 生成 左布比卡因
  参考文献：
  名称：

  部分氟化的N-烷基取代的哌啶-2-羧酰胺对药理学性质的影响

  摘要：

  通过选择性地将1-3个氟原子引入n-丙基和n中，研究了N-烷基-哌啶-2-羧酰胺的药理相关特性的调节局部麻醉药罗哌卡因和左旋布比卡因的叔丁基侧链。附近氟取代基对碱的调节本质上是加和的，并且表现出随氟与碱中心之间的拓扑距离而变的指数衰减。中性哌啶衍生物的固有亲脂性显示出对连接至中性杂芳基系统的部分氟化烷基的特征响应。但是，附近的氟取代基引起的碱度降低会影响中性pH值的亲脂性，因此所有部分氟化的衍生物的亲脂性都比其未氟化的母体相似或更高。发现水溶性与亲脂性成反比，并且与晶体堆积能有很大关系，如熔点温度的变化所示。发现所有氟化衍生物在人肝微粒体中都更容易被氧化，降解速率与亲脂性增加相关。因为哌啶-2-羧酰胺核心是手性的，所以与对映异构体配对N-烷基是非对映异构的。虽然对于碱性或亲脂性几乎观察不到对这种立体异构的反应，但是对于熔点温度和氧化降解观察到更明显的变化。

  DOI：

  10.1002/cmdc.201600325
• 作为产物：
  描述：

  L-哌啶-2-甲酸 在 N-甲基吗啉 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 水 、 丙酮 为溶剂， 生成 (S)-N-Boc-piperidine-2-carboxylic acid 2,6-dimethylphenyl amide
  参考文献：
  名称：

  Synthesis of 2-piperidinecarboxylic acid derivatives as potential anticonvulsants

  摘要：

  A variety of 2-piperidinecarboxamides were synthesized and evaluated for anticonvulsant activity using the MES and sc PTZ tests in mice and rats. Neurotoxicity was determined by the rotorod test. Several N-(benzyl)-2-piperidinecarboxamides exhibited potent MES activity in mice [2-CF3 14, ED50 = 29 mg/kg; 3-F 16, ED50 = 31 mg/kg; and 3-CF3 17, ED50 = 24 mg/kg]. The most active compounds in the MES test in mice were the 2,6-dimethylanilides [(R,S)-34, ED50 = 5.8 mg/kg; (R)-35, ED50 = 5.7 mg/kg; and (S)-36, ED50 = 14.8 mg/kg]. The enantiomer (S)-36 was about two-fold less potent in the MES test than (R)-35 and also was less neurotoxic. Acylation of the piperidine ring nitrogen of 12 and 34 led to a decrease in the MES activity. In the N-(alpha-methylbenzyl)-2-piperidine-carboxamides, the stereochemistry at either the 2-position of the piperidine ring or at the alpha-position of the N-(alpha-methylbenzyl) group does not significantly affect MES activity. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(99)80072-5

文献信息

• Highly Enantioselective Catalytic Dynamic Resolution of <i>N</i>-Boc-2-lithiopiperidine: Synthesis of (<i>R</i>)-(+)-<i>N-</i>Boc-Pipecolic Acid, (<i>S</i>)-(−)-Coniine, (<i>S</i>)-(+)-Pelletierine, (+)-β-Conhydrine, and (<i>S</i>)-(−)-Ropivacaine and Formal Synthesis of (−)-Lasubine II and (+)-Cermizine C
  作者：Timothy K. Beng、Robert E. Gawley

  DOI：10.1021/ja105772z

  日期：2010.9.8

  syntheses of both enantiomers of 2-substituted piperidines using a wide range of electrophiles. The CDR has been applied to the synthesis of (R)- and (S)-pipecolic acid derivatives, (+)-beta-conhydrine, (S)-(+)-pelletierine, and (S)-(-)-ropivacaine and the formal synthesis of (-)-lasubine II and (+)-cermizine C.

  在 TMEDA 存在下，使用手性配体 8 或其非对映异构体 9 的 rac-2-锂硫-N-Boc-哌啶催化动态拆分 (CDR) 导致使用广泛的 2-取代哌啶的两种对映体的高度对映选择性合成亲电试剂的范围。CDR 已应用于 (R)- 和 (S)-哌啶酸衍生物、(+)-β-conhydrine、(S)-(+)-pelletierine 和 (S)-(-)-ropivacaine 的合成(-)-lasubine II 和 (+)-cermizine C 的正式合成。
• Synthesis of 2-piperidinecarboxylic acid derivatives as potential anticonvulsants
  作者：Bin Ho、Prabha M. Venkatarangan、Sharon F. Cruse、Christine N. Hinko、Peter H. Andersen、Albert M. Crider、Ahmad A. Adloo、David S. Roane、James P. Stables

  DOI：10.1016/s0223-5234(99)80072-5

  日期：1998.1

  A variety of 2-piperidinecarboxamides were synthesized and evaluated for anticonvulsant activity using the MES and sc PTZ tests in mice and rats. Neurotoxicity was determined by the rotorod test. Several N-(benzyl)-2-piperidinecarboxamides exhibited potent MES activity in mice [2-CF3 14, ED50 = 29 mg/kg; 3-F 16, ED50 = 31 mg/kg; and 3-CF3 17, ED50 = 24 mg/kg]. The most active compounds in the MES test in mice were the 2,6-dimethylanilides [(R,S)-34, ED50 = 5.8 mg/kg; (R)-35, ED50 = 5.7 mg/kg; and (S)-36, ED50 = 14.8 mg/kg]. The enantiomer (S)-36 was about two-fold less potent in the MES test than (R)-35 and also was less neurotoxic. Acylation of the piperidine ring nitrogen of 12 and 34 led to a decrease in the MES activity. In the N-(alpha-methylbenzyl)-2-piperidine-carboxamides, the stereochemistry at either the 2-position of the piperidine ring or at the alpha-position of the N-(alpha-methylbenzyl) group does not significantly affect MES activity. (C) Elsevier, Paris.
• Effect of Partially Fluorinated<i>N</i>-Alkyl-Substituted Piperidine-2-carboxamides on Pharmacologically Relevant Properties
  作者：Raffael Vorberg、Nils Trapp、Daniel Zimmerli、Björn Wagner、Holger Fischer、Nicole A. Kratochwil、Manfred Kansy、Erick M. Carreira、Klaus Müller

  DOI：10.1002/cmdc.201600325

  日期：2016.10.6

  energies, as indicated by variations in melting point temperatures. All fluorinated derivatives were found to be somewhat more readily oxidized in human liver microsomes, the rates of degradation correlating with increasing lipophilicity. Because the piperidine‐2‐carboxamide core is chiral, pairs with enantiomeric N‐alkyl groups are diastereomeric. While little response to such stereoisomerism was observed

  通过选择性地将1-3个氟原子引入n-丙基和n中，研究了N-烷基-哌啶-2-羧酰胺的药理相关特性的调节局部麻醉药罗哌卡因和左旋布比卡因的叔丁基侧链。附近氟取代基对碱的调节本质上是加和的，并且表现出随氟与碱中心之间的拓扑距离而变的指数衰减。中性哌啶衍生物的固有亲脂性显示出对连接至中性杂芳基系统的部分氟化烷基的特征响应。但是，附近的氟取代基引起的碱度降低会影响中性pH值的亲脂性，因此所有部分氟化的衍生物的亲脂性都比其未氟化的母体相似或更高。发现水溶性与亲脂性成反比，并且与晶体堆积能有很大关系，如熔点温度的变化所示。发现所有氟化衍生物在人肝微粒体中都更容易被氧化，降解速率与亲脂性增加相关。因为哌啶-2-羧酰胺核心是手性的，所以与对映异构体配对N-烷基是非对映异构的。虽然对于碱性或亲脂性几乎观察不到对这种立体异构的反应，但是对于熔点温度和氧化降解观察到更明显的变化。