4-(N-甲基-N-苄基)氨基哌啶 | 76167-62-9

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(N-甲基-N-苄基)氨基哌啶
• 中文别名: N-苄基-N-甲基哌啶-4-胺2HCL
• 英文名称: N-benzyl-N-methylpiperidin-4-amine
• 英文别名: 4-(N-benzyl-N-methylamino)-piperidine
• CAS: 76167-62-9
• 化学式: C₁₃H₂₀N₂
• 分子量: 204.315
• InChiKey: JQSWRIGANADNJD-UHFFFAOYSA-N

物化性质

• 沸点：
  118-120 °C(Press: 0.1 Torr)
• 密度：
  1.01±0.1 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：
  0.54
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933399090

制备方法与用途

制备

4-(N-甲基-N-苄基)氨基哌啶的制备如下：在室温下，向1,4-二噁烷/甲醇（1/1、8.0 mL）混合溶液中加入4-（N-苄基-N-甲基氨基）哌啶-1-甲酸叔丁基酯（1.00 g，3.28 mmol），再滴加氯化氢的1,4-二噁烷溶液（4.0 N、3.28 mL，13.1 mmol）。将反应液在相同温度下搅拌6小时。减压浓缩后，加入饱和碳酸氢钠水溶液，并用氯仿萃取有机层。滤液经无水硫酸钠干燥并过滤后，再次减压浓缩。最后，通过快速色谱法（硅胶、氯仿/甲醇）纯化残渣，得到4-(N-甲基-N-苄基)氨基哌啶（0.650 g，0.318 mmol，收率97%）。

应用

4-(N-甲基-N-苄基)氨基哌啶可用作医药合成中间体。若不慎吸入4-溴喹啉-6-羧酸，请立即将患者移至新鲜空气处。

反应信息

• 作为反应物：
  描述：

  4-(N-甲基-N-苄基)氨基哌啶 在 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium(II) hydroxide 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 氢气 、 sodium t-butanolate 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 7.0h， 生成 1-(6-Methoxypyridin-3-yl)-N-methylpiperidin-4-amine
  参考文献：
  名称：

  Substituted Benzamide Compounds

  摘要：

  对应于式(I)的取代苯甲酰胺化合物，其中R5、R6、R7、R8、a、b、c、d、t、D和X具有定义的含义，其制备方法，包括这些化合物的药物组合物，以及使用这些化合物治疗疼痛和其他至少部分通过激肽酶1受体介导的疾病的方法。

  公开号：

  US20120071461A1
• 作为产物：
  描述：

  1-叔丁氧羰基-4-甲氨基哌啶 在 三乙酰氧基硼氢化钠 、 溶剂黄146 、 三氟乙酸 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 生成 4-(N-甲基-N-苄基)氨基哌啶
  参考文献：
  名称：

  新型抗锥虫化合物的设计、合成和评价。

  摘要：

  人类非洲锥虫病 (HAT) 是一种致命的被忽视的热带疾病，由原生动物寄生虫布氏锥虫引起。在筛选一系列不同的含氮杂环化合物的过程中，我们发现了两种新化合物，它们含有育亨宾和 Corynanthe 生物碱的四环核心，它们是布氏杆菌增殖和布氏杆菌甲硫氨酰-tRNA 合成酶 (TbMetRS) 活性的有效抑制剂。受这些关键发现的启发，我们制备了几个新系列的羟烷基 δ-内酰胺、δ-内酰胺和哌啶类似物，并测试了它们的抗锥虫活性。许多抑制剂对布氏锥虫的作用比这些最初的抑制剂更有效，其中一种羟烷基 δ-内酰胺衍生物在我们的测定中有效 25 倍。令人惊讶的是，这些活性化合物中的大多数都未能抑制 TbMetRS。

  DOI：

  10.1016/j.tet.2020.131086

文献信息

• CYCLIC AMINE DERIVATIVE AND PHARMACEUTICAL USE THEREOF
  申请人：Toray Industries, Inc.

  公开号：US20160194302A1

  公开（公告）日：2016-07-07

  A compound exerts a strong analgesic effect against pain, in particular, neuropathic pain and/or fibromyalgia syndrome. The cyclic amine derivative is represented by formula, a prodrug thereof or a pharmacologically acceptable salt thereof: wherein A represents a group represented by Formula (IIa), (IIb) or (IIc): wherein R 3 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, R 4 represents a hydrogen atom or an alkylcarbonyl group having 2 to 6 carbon atoms or an alkyl group having 1 to 6 carbon atoms and optionally substituted with an alkylcarbonylamino group having 2 to 6 carbon atoms and n represents 1 or 2, in which when R 3 and R 4 each independently represent an alkyl group having 1 to 6 carbon atoms, R 1 represents an alkyl group having 1 to 6 carbon atoms and substituted with a hydroxyl group, an amino group or a carboxyl group.

  一种化合物对疼痛，特别是神经病性疼痛和/或纤维肌痛综合征具有强烈的镇痛作用。该环胺衍生物由以下公式代表，其前药或药理学上可接受的盐： 其中A代表由公式（IIa）、（IIb）或（IIc）表示的基团： 其中 R 3 代表氢原子或具有1至6个碳原子的烷基基团，R 4 代表氢原子或具有2至6个碳原子的烷基羰基基团或具有1至6个碳原子的烷基基团，并且可选择地被取代为具有2至6个碳原子的烷基羰基氨基基团，n代表1或2，在其中当R 3 和R 4 各自独立地代表具有1至6个碳原子的烷基基团时，R 1 代表具有1至6个碳原子的烷基基团，并且被取代为具有羟基、氨基或羧基。
• Fluorination of 3-(3-(Piperidin-1-yl)propyl)indoles and 3-(3-(Piperazin-1-yl)propyl)indoles Gives Selective Human 5-HT_1D Receptor Ligands with Improved Pharmacokinetic Profiles
  作者：Monique B. van Niel、Ian Collins、Margaret S. Beer、Howard B. Broughton、Susan K. F. Cheng、Simon C. Goodacre、Anne Heald、Karen L. Locker、Angus M. MacLeod、Denise Morrison、Christopher R. Moyes、Desmond O'Connor、Andrew Pike、Michael Rowley、Michael G. N. Russell、Balbinder Sohal、Josephine A. Stanton、Steven Thomas、Hugh Verrier、Alan P. Watt、José L. Castro

  DOI：10.1021/jm981133m

  日期：1999.6.1

  It has previously been reported that a 3-(3-(piperazin-1-yl)propyl)indole series of 5-HT1D receptor ligands have pharmacokinetic advantages over the corresponding 3-(3-(piperidin-1-yl)propyl)indole series and that the reduced pKa of the piperazines compared to the piperidines may be one possible explanation for these differences. To investigate this proposal we have developed versatile synthetic strategies

  以前已经报道过，3-（3-（哌嗪-1-基）丙基）吲哚系列的5-HT1D受体配体比相应的3-（3-（哌啶-1-基）丙基）吲哚具有药代动力学优势。与哌啶相比，哌嗪的pKa降低可能是这些差异的一种可能解释。为了研究该提议，我们开发了将氟掺入这些配体中的通用合成策略，生产出一系列新的4-氟哌啶，3-氟-4-氨基哌啶，以及哌嗪和哌啶衍生物，其丙基连接基中带有一个或两个氟。 。鉴定了对5-HT1D受体保持高亲和力和选择性并在体外显示激动剂功效的配体。发现掺入氟可显着降低化合物的pKa，
• [EN] PYRROLOPYRIMIDINE DERIVATIVES USEFUL AS MODULATORS OF MULTIDRUG RESISTANCE<br/>[FR] DERIVES DE PYRROLOPYRIMIDINE POUVANT ETRE UTILISES EN TANT QUE MODULATEURS DE LA MULTIRESISTANCE AUX MEDICAMENTS
  申请人：XENOVA LTD

  公开号：WO2004065389A1

  公开（公告）日：2004-08-05

  A compound which is a pyrrolopyrimidine of formula (I) wherein: R1 is selected from R9 and halogen; R2 is NR6R7; R3 is selected from H, C1-C6 alkyl which is unsubstituted or substituted and -(CH2) nAr; R4 is selected from H, C1-C6 alkyl and -(CH2)„ Ar; or R3 and R4 form, together with the N and C atoms to which they are attached, a fused five-, six-, seven- or eight-membered N-containing saturated ring which is unsubstituted or substituted; R5 is selected from CN, C02R9, C(O)NR10R11, -(CH2)nOH, -(CH2)nR10Rn, -C=CH, -C(S)NR10R11, -C(NH2)=NOR9, -C(R9)=NOR9, -C(NH2)NH, -C(O)R9 and an unsaturated 5- or 6-membered heterocyclic group which contains 1, 2 or 3 heteroatoms selected from N, O and S and which is unsubstituted or substituted; R6 and R7, which are the same or different, are selected from C1-C6 alkyl which is unsubstituted or substituted, -(CH2)nX and -(CH2)nAr; or R6 and R7 form, together with the nitrogen atom to which they are attached, a saturated five-, six-, seven- or eight-membered heterocyclic group which contains one nitrogen atom and 0 or from 1 to 3 additional heteroatoms selected from N, O and S, which is unsubstituted or substituted and which optionally contains one or two bridgehead atoms; R10 and R11, which are the same or different, are selected from H, C1-C6 alkyl which is unsubstituted or substituted, -(CH2)nC3-C10 cycloalkyl and -(CH2) nAr; or R10 and R11 form, together with the nitrogen atom to which they are attached, a saturated five or six membered heterocyclic group which contains a nitrogen atom and 0 or from to 3 additional heteroatoms selected from O, S and N, which is unsubstituted or substituted and which is optionally fused to a benzene ring which is unsubstituted or substituted; n is the same or different when more than one is present within a given substituent group and is 0 or an integer of from 1 to 6; X is selected from -CN, -C02R9 and -NR10R11; R9 is the same or different when more than one is present within a given substituent group and is selected from -H, -QAr, -(CH2) nAr, C1-C6 alkyl which is unsubstituted or substituted and -(CH2) nC3-C10cycloalkyl, wherein the cycloalkyl moiety is optionally fused to a benzene ring which is unsubstituted or substituted; Q is C2-C6 alkenylene or alkynylene; and Ar is an unsaturated C6-C10 membered carbocyclic group or an unsaturated 5-11 membered heterocyclic group, which groups are unsubstituted or substituted; or a pharmaceutically acceptable salt thereof. These compounds have activity as inhibitors of MRP (multidrug resistant protein) and may thus be used to modulate multidrug resistance, for instance in potentiating the cytotoxicity of a chemotherapeutic agent.

  一种具有以下结构式(I)的吡咯吡嘧啶化合物，其中：R1从R9和卤素中选择；R2为NR6R7；R3从H、未取代或取代的C1-C6烷基和-(CH2) nAr中选择；R4从H、C1-C6烷基和-(CH2) nAr中选择；或者R3和R4与它们连接的N和C原子一起形成未取代或取代的融合的含氮饱和环，该环为五、六、七或八元环；R5从CN、C02R9、C(O)NR10R11、-(CH2)nOH、-(CH2)nR10Rn、-C=CH、-C(S)NR10R11、-C(NH2)=NOR9、-C(R9)=NOR9、-C(NH2)NH、-C(O)R9和一个含有1、2或3个异原子（N、O和S）且未取代或取代的不饱和5-或6元杂环基中选择；R6和R7相同或不同，从未取代或取代的C1-C6烷基、-(CH2)nX和-(CH2)nAr中选择；或者R6和R7与它们连接的氮原子一起形成含有一个氮原子和0或1至3个额外异原子（N、O和S）的饱和五、六、七或八元杂环基，该环未取代或取代，可选地包含一个或两个桥头原子；R10和R11相同或不同，从未取代或取代的H、C1-C6烷基、-(CH2)nC3-C10环烷基和-(CH2)nAr中选择；或者R10和R11与它们连接的氮原子一起形成含有一个氮原子和0或1至3个额外异原子（O、S和N）的饱和五或六元杂环基，该环未取代或取代，可选地与未取代或取代的苯环融合；n在给定取代基中的多个存在时相同或不同，为0或1至6的整数；X从-CN、-C02R9和-NR10R11中选择；R9在给定取代基中的多个存在时相同或不同，从-H、-QAr、-(CH2)nAr、未取代或取代的C1-C6烷基和-(CH2)nC3-C10环烷基中选择，其中环烷基部分可选地与未取代或取代的苯环融合；Q为C2-C6烯基或炔基；Ar为未取代或取代的不饱和C6-C10环烷基或不饱和5-11元杂环基，或其药学上可接受的盐。这些化合物具有作为MRP（多药耐药蛋白）抑制剂的活性，因此可用于调节多药耐药性，例如增强化疗药物的细胞毒性。
• Azetidine, pyrrolidine and piperidine derivatives
  申请人：Merck Sharpe & Dohme Ltd.

  公开号：US05998440A1

  公开（公告）日：1999-12-07

  A class of substituted azetidine, pyrrolidine and piperidine derivatives, linked by a fluoro-substituted alkylene chain to a fused bicyclic heteroaromatic moiety such as indolyl, are selective agonists of 5-HT.sub.1 -like receptors, being potent agonists of the human 5-HT.sub.1D.alpha. receptor subtype while possessing at least a 10-fold selective affinity for the 5-HT.sub.1D.alpha. receptor subtype relative to the 5-HT.sub.1D.beta. subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT.sub.1D receptors is indicated, while eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT.sub.1D receptor agonists.

  一类取代的氮杂环丙烷、吡咯烷和哌啶衍生物，通过含氟取代的烷基链连接到融合的双环杂芳基团（如吲哚基），是5-HT.sub.1-类受体的选择性激动剂，是人类5-HT.sub.1Dα受体亚型的有效激动剂，同时相对于5-HT.sub.1Dβ亚型具有至少10倍的选择性亲和力；因此，在治疗和/或预防临床疾病，特别是偏头痛及相关疾病方面具有用途，适用于需要5-HT.sub.1D受体亚型选择性激动剂的情况，而且引起的副作用更少，尤其是不良心血管事件，相对于与非亚型选择性5-HT.sub.1D受体激动剂相关的情况。
• Azetidine, pyrrolidine and piperidine derivatives as 5-HT.sub.1D
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US06127388A1

  公开（公告）日：2000-10-03

  A class of substituted azetidine, pyrrolidine and piperidine derivatives of Formula I are selective agonists of 5-HT.sub.1 -like receptors, being potent agonists of the human 5-HT.sub.1D.alpha. receptor subtype whilst possessing at least a 10-fold selective affinity for the 5-HT.sub.1D.alpha. receptor subtype relative to the 5-HT.sub.1D.beta. subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT.sub.1D receptors is indicated, whilst eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT.sub.1D receptor agonists. ##STR1##

  公式I中的一类取代的氮杂环化合物，包括氮杂环丙烷，吡咯烷和哌嗪衍生物，是5-HT.sub.1-类受体的选择性激动剂，是人类5-HT.sub.1D.alpha.受体亚型的有效激动剂，同时相对于5-HT.sub.1D.beta.亚型具有至少10倍的选择亲和力；因此，它们在治疗和/或预防临床情况方面是有用的，特别是偏头痛和相关疾病，需要5-HT.sub.1D受体亚型选择性激动剂，同时引起的副作用较少，特别是不良心血管事件，比与非亚型选择性5-HT.sub.1D受体激动剂相关的副作用更少。##STR1##