4-allyl-N,1-dibenzylpiperidin-4-amine | 336108-92-0

• 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: 4-allyl-N,1-dibenzylpiperidin-4-amine
• 英文别名: N,1-dibenzyl-4-prop-2-enylpiperidin-4-amine
• CAS: 336108-92-0
• 化学式: C₂₂H₂₈N₂
• 分子量: 320.478
• InChiKey: NFFOYNJXXFMPSJ-UHFFFAOYSA-N

物化性质

• 沸点：
  429.7±40.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-allyl-N,1-dibenzylpiperidin-4-amine 在 dichloro[1,3-bis(2-methylphenyl)-2-imidazolidinylidene](2-isopropoxyphenyl-methylene) ruthenium(II) 、 potassium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 、 乙腈 为溶剂， 反应 81.5h， 生成 1,9-dibenzyl-N-methyl-1,9-diazaspiro[5.5]undec-3-ene-3-carboxamide
  参考文献：
  名称：

  Synthesis and evaluation of heteroaryl substituted diazaspirocycles as scaffolds to probe the ATP-binding site of protein kinases

  摘要：

  With the success of protein. kinase inhibitors as drugs to target cancer, there is a continued need for new kinase inhibitor scaffolds. We have investigated the synthesis and kinase inhibition of new heteroaryl-substituted diazaspirocyclic compounds that mimic ATP. Versatile syntheses of substituted diazaspirocycles through ring-closing metathesis were demonstrated. Diazaspirocycles directly linked to heteroaromatic hinge binder groups provided ligand efficient inhibitors of multiple kinases, suitable as starting points for further optimization. The binding modes of representative diazaspirocyclic motifs were confirmed by protein crystallography. Selectivity profiles were influenced by the hinge binder group and the interactions of basic nitrogen atoms in the scaffold with acidic side-chains of residues in the ATP pocket. The introduction of more complex substitution to the diazaspirocycles increased potency and varied the selectivity profiles of these initial hits through engagement of the P-loop and changes to the spirocycle conformation, demonstrating the potential of these core scaffolds for future application to kinase inhibitor discovery. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.07.021
• 作为产物：
  描述：

  N-(1-benzylpiperidin-4-ylidene)-1-phenylmethanamine 、 烯丙基溴化镁 以 乙醚 为溶剂， 反应 4.0h， 以89%的产率得到4-allyl-N,1-dibenzylpiperidin-4-amine
  参考文献：
  名称：

  从4-亚氨基哌啶两步合成新的1,2,4,5-四氢螺-[3 H -2-苯并ze庚因-3,4'-哌啶]

  摘要：

  新的螺[3 H -2-苯并ze庚因-3,4'-哌啶]及其前体N-取代的4-烯丙基-4- N-苄基-氨基哌啶已从容易获得的4-亚氨基哌啶中制备为潜在的精神病药物，通过一系列反应，包括亲核添加格氏试剂和布朗斯台德酸介导的分子内环化反应。已经在白化病小鼠中测试了所制备的某些化合物的自发运动活性。通过ir和1 H nmr光谱学和cg-ms光谱对所有制备的化合物进行表征。

  DOI：

  10.1002/jhet.5570380405

文献信息

• Synthesis of Four Novel Natural Product Inspired Scaffolds for Drug Discovery
  作者：Ian D. Jenkins、Fabienne Lacrampe、Justin Ripper、Lilian Alcaraz、Phuc Van Le、George Nikolakopoulos、Priscila de Almeida Leone、Rodney H. White、Ronald J. Quinn

  DOI：10.1021/jo802456w

  日期：2009.2.6

  Inspired by the novel spiro structures of a number of bioactive natural products such as the histrionicotoxins, a series of novel spiro scaffolds have been designed and robust syntheses developed. The scaffolds are ready-to-use building blocks and can be easily prepared on a 5−20 g scale. They contain two amino groups (one Boc-protected) and have been designed for ease of conversion to a lead generation

  受许多生物活性天然产物（如组织毒素）的新型螺旋结构的启发，已设计了一系列新型螺旋支架，并开发了稳健的合成方法。脚手架是现成的构建基块，可以轻松制备成5-20克的规模。它们含有两个氨基基团（一个受Boc保护的氨基基团），并且使用酰胺形成或还原性胺化步骤进行了设计，可轻松转换成铅生成库。以RCM为关键步骤，完成了1,9-二氮杂螺[5.5]十一烷和3,7-二氮杂螺[5.6]十二烷环的合成。据报道，有一种简单的后处理程序可以去除高度着色的钌残留物。1,8-二氮杂螺[4.的合成。5]癸烷支架是通过在酸性条件下使用溴介导的相应的4-氨基丁烯中间体的5-内基环化来实现的。这是要报道的这类环化反应的第一个例子。提出了一种新的机理，涉及从最初形成的溴离子到相邻氮原子的溴转移反应，这是这种反应在“正常”溴化条件下失败的原因。据报道，1-酰基-1，9-二氮杂螺[5.5]十一烷的异常重新排列为相应的9-酰基-1，9-二氮杂螺[5
• Synthesis and evaluation of heteroaryl substituted diazaspirocycles as scaffolds to probe the ATP-binding site of protein kinases
  作者：Charlotte E. Allen、Chiau L. Chow、John J. Caldwell、Isaac M. Westwood、Rob L. M. van Montfort、Ian Collins

  DOI：10.1016/j.bmc.2013.07.021

  日期：2013.9

  With the success of protein. kinase inhibitors as drugs to target cancer, there is a continued need for new kinase inhibitor scaffolds. We have investigated the synthesis and kinase inhibition of new heteroaryl-substituted diazaspirocyclic compounds that mimic ATP. Versatile syntheses of substituted diazaspirocycles through ring-closing metathesis were demonstrated. Diazaspirocycles directly linked to heteroaromatic hinge binder groups provided ligand efficient inhibitors of multiple kinases, suitable as starting points for further optimization. The binding modes of representative diazaspirocyclic motifs were confirmed by protein crystallography. Selectivity profiles were influenced by the hinge binder group and the interactions of basic nitrogen atoms in the scaffold with acidic side-chains of residues in the ATP pocket. The introduction of more complex substitution to the diazaspirocycles increased potency and varied the selectivity profiles of these initial hits through engagement of the P-loop and changes to the spirocycle conformation, demonstrating the potential of these core scaffolds for future application to kinase inhibitor discovery. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
• Two-step synthesis of new 1,2,4,5-tetrahydrospiro-[3<i>H</i>-2-benzazepine-3,4′-piperidines] from 4-iminopiperidines
  作者：Palma R. Alirio、Sandra Salas、Vladimir Kouznetsov、Elena Stashenko、Montenegro N. Gisela、Fontela G. Angel

  DOI：10.1002/jhet.5570380405

  日期：2001.7

  New spiro[3H-2-benzazepine-3,4′-piperidines] and their precursors, N-substituted 4-allyl-4-N-benzyl-aminopiperidines, have been prepared as potential psychotic agents from readily available 4-iminopiperidines, by a sequence of reactions that included nucleophilic addition of Grignard reagents and Bronsted acid-mediated intramolecular cyclisation. Some of the compounds prepared have been tested in albine

  新的螺[3 H -2-苯并ze庚因-3,4'-哌啶]及其前体N-取代的4-烯丙基-4- N-苄基-氨基哌啶已从容易获得的4-亚氨基哌啶中制备为潜在的精神病药物，通过一系列反应，包括亲核添加格氏试剂和布朗斯台德酸介导的分子内环化反应。已经在白化病小鼠中测试了所制备的某些化合物的自发运动活性。通过ir和1 H nmr光谱学和cg-ms光谱对所有制备的化合物进行表征。