1-chloro-4-methylpiperidine | 58310-12-6

• 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: 1-chloro-4-methylpiperidine
• 英文别名: 4-methyl-N-chloropiperidine；1-chloro-4-methyl-piperidine；1-Chlor-4-methyl-piperidin；N-Chlor-4-methyl-piperidin；4-Methyl-N-chlorpiperidin；4-Chlor-1-methylpiperidine
• CAS: 58310-12-6
• 化学式: C₆H₁₂ClN
• 分子量: 133.621
• InChiKey: FZFGYZBSIZFURA-UHFFFAOYSA-N

物化性质

• 沸点：
  156.9±23.0 °C(Predicted)
• 密度：
  1.04±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-chloro-4-methylpiperidine 在 sodium methylate 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 0.75h， 生成 2,3,4,5-四氢-4-甲基吡啶
  参考文献：
  名称：

  Restriction of the Conformational Dynamics of the Cyclic Acyldepsipeptide Antibiotics Improves Their Antibacterial Activity

  摘要：

  The cyclic acyldepsipeptide (ADEP) antibiotics are a new class of antibacterial agents that kill bacteria via a mechanism that is distinct from all clinically used drugs. These molecules bind and dysregulate the activity of the ClpP peptidase. The potential of these antibiotics as antibacterial drugs has been enhanced by the elimination of pharmacological liabilities through medicinal chemistry efforts. Here, we demonstrate that the ADEP conformation observed in the ADEP-ClpP crystal structure is fortified by transannular hydrogen bonding and can be further stabilized by judicious replacement of constituent amino acids within the peptidolactone core structure with more conformationally constrained counterparts. Evidence supporting constraint of the molecule into the bioactive conformer was obtained by measurements of deuterium-exchange kinetics of hydrogens that were proposed to be engaged in transannular hydrogen bonds. We show that the rigidified ADEP analogs bind and activate ClpP at lower concentrations in vitro. Remarkably, these compounds have up to 1200-fold enhanced antibacterial activity when compared to those with the peptidolactone core structure common to two ADEP natural products. This study compellingly demonstrates how rational modulation of conformational dynamics may be used to improve the bioactivities of natural products.

  DOI：

  10.1021/ja410385c
• 作为产物：
  描述：

  4-甲基哌啶 在 sodium hypochlorite 作用下， 以 甲基叔丁基醚 、 叔丁醇 为溶剂， 反应 1.0h， 生成 1-chloro-4-methylpiperidine
  参考文献：
  名称：

  Restriction of the Conformational Dynamics of the Cyclic Acyldepsipeptide Antibiotics Improves Their Antibacterial Activity

  摘要：

  The cyclic acyldepsipeptide (ADEP) antibiotics are a new class of antibacterial agents that kill bacteria via a mechanism that is distinct from all clinically used drugs. These molecules bind and dysregulate the activity of the ClpP peptidase. The potential of these antibiotics as antibacterial drugs has been enhanced by the elimination of pharmacological liabilities through medicinal chemistry efforts. Here, we demonstrate that the ADEP conformation observed in the ADEP-ClpP crystal structure is fortified by transannular hydrogen bonding and can be further stabilized by judicious replacement of constituent amino acids within the peptidolactone core structure with more conformationally constrained counterparts. Evidence supporting constraint of the molecule into the bioactive conformer was obtained by measurements of deuterium-exchange kinetics of hydrogens that were proposed to be engaged in transannular hydrogen bonds. We show that the rigidified ADEP analogs bind and activate ClpP at lower concentrations in vitro. Remarkably, these compounds have up to 1200-fold enhanced antibacterial activity when compared to those with the peptidolactone core structure common to two ADEP natural products. This study compellingly demonstrates how rational modulation of conformational dynamics may be used to improve the bioactivities of natural products.

  DOI：

  10.1021/ja410385c

文献信息

• Directed Copper-Catalyzed Intermolecular Aminative Difunctionalization of Unactivated Alkenes
  作者：Yang Li、Yujie Liang、Junchao Dong、Yi Deng、Chunyang Zhao、Zhongmin Su、Wei Guan、Xihe Bi、Qun Liu、Junkai Fu

  DOI：10.1021/jacs.9b07607

  日期：2019.11.20

  intermolecular aminohalogenation reactions and a three-component aminoazidation reaction of unactivated alkenes with dialkylamino source were successively achieved in a remarkable regio- and stereoselective manner. These reactions were performed under neutral conditions and maintained excellent functional group tolerance toward a wide range of N-halodialkylamines and unactivated alkenes. Further mechanistic

  报道了以 N-卤代二烷基胺作为末端二烷基氨基源的未活化烯烃的多种铜催化分子间氨基化双官能化。连接在烯烃底物上的双齿助剂是至关重要的，它可以促进未活化的烯烃迁移插入氨基自由基-金属络合物中，并稳定所得的高价铜中间体以进行进一步的转化。通过采用该策略，以显着的区域选择性和立体选择性方式相继实现了未活化烯烃与二烷基氨基的分子间氨基卤化反应和三组分氨基叠氮化反应。这些反应是在中性条件下进行的，并且对各种 N-卤代二烷基胺和未活化的烯烃保持优异的官能团耐受性。进一步的机理研究和 DFT 计算支持 CC 双键协同迁移插入胺基自由基 - 金属络合物以形成 Cu(III) 中间体。
• [EN] COMPOUNDS AND COMPOSITIONS AS MODULATORS OF GPR119 ACTIVITY<br/>[FR] COMPOSÉS ET COMPOSITIONS SERVANT DE MODULATEURS DE L'ACTIVITÉ DE GPR119
  申请人：IRM LLC

  公开号：WO2009126535A1

  公开（公告）日：2009-10-15

  The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of GPR119; such as, but not limited to, diabetes, obesity and associated metabolic disorders. Formula (I) is a compound, in which A can have up to 2 ring -CH2- group substituted with -C(O)- and can be partially unsaturated with up to 2 double bonds; Wi and W2 are independently selected from CR10 and N; wherein R10 is selected from hydrogen and C1_6alkyl; Yi is selected from NRn, O and S; wherein Rn is selected from hydrogen and C1_ 6alkyl; Y2 and Y3 are independently selected from CH and N; Y4 is selected from CH2, OCH2 and NR15; wherein R15 is selected from hydrogen and C1_6alkyl; or the pharmaceutically acceptable salts thereof.

  本发明提供化合物、包含这些化合物的药物组合物以及使用这些化合物治疗或预防与GPR119活性相关的疾病或疾病，例如但不限于糖尿病、肥胖症和相关代谢障碍的方法。公式（I）是一种化合物，其中A可以有高达2个环-CH2-基团被-C（O）-取代，并且可以部分不饱和，具有高达2个双键；Wi和W2分别选自CR10和N；其中R10选自氢和C1_6烷基；Yi选自NRn、O和S；其中Rn选自氢和C1_6烷基；Y2和Y3分别选自CH和N；Y4选自 、O 和NR15；其中R15选自氢和C1_6烷基；或其药学上可接受的盐。
• Carbonylative coupling of <i>N</i>-chloroamines with alcohols: synthesis of esterification reagents
  作者：Zhiping Yin、Zechao Wang、Xiao-Feng Wu

  DOI：10.1039/c8ob00462e

  日期：——

  the carbonylative synthesis of carbamates. Starting from N-chloroamines and alcohols, with copper or Pd/C as the catalyst, the corresponding carbamates were produced in moderate to good yields. No additional oxidant or base is needed in this system. Notably, the produced benzotriazole-carboxylates can be used as esterification reagents.

  在这里，我们报告了一种氨基甲酸酯羰基合成的新方法。从N-氯胺和醇开始，以铜或Pd / C为催化剂，以中等至良好的产率生产相应的氨基甲酸酯。在该系统中不需要额外的氧化剂或碱。值得注意的是，所产生的苯并三唑-羧酸盐可用作酯化剂。
• Copper-Catalyzed Carbonylative Cross-Coupling of Arylboronic Acids with<i>N</i>-Chloroamines for the Synthesis of Aryl Amides
  作者：Zhiping Yin、Zechao Wang、Wanfang Li、Xiao-Feng Wu

  DOI：10.1002/ejoc.201700352

  日期：2017.4.3

  A novel copper-catalyzed carbonylative cross-coupling between N-chloroamines and arylboronics acids has been developed. With copper(I) oxide as the catalyst, various desired amide compounds were produced in moderate to good yields. Functional groups such as iodide and alkene are tolerated. Notably, this is the first example of a copper-catalyzed aminocarbonylation with N-chloroamines.

  N-氯胺和芳基硼酸之间的新型铜催化羰基化交叉偶联已被开发出来。以氧化铜 (I) 为催化剂，以中等至良好的收率生产了各种所需的酰胺化合物。可耐受碘化物和烯烃等官能团。值得注意的是，这是铜催化氨基羰基化与 N-氯胺的第一个例子。
• [(Pyrimidinyl-2)-aminoalkyl]-1 pipéridines, leur préparation et leur application en thérapeutique
  申请人：SYNTHELABO

  公开号：EP0307303A1

  公开（公告）日：1989-03-15

  Dérivés pyrimidinylaminés de pipéridine, répondant à la formule (I) dans laquelle X représente un radical (CH₂)₂, CH = CH ou CH₂-CO, Y représente le radical CH = CH ou un atome de soufre, n est 2,3 ou 4, R₁ est un atome d'hydrogène ou d'halogène, R₂ est un atome d'hydrogène ou un radical (C₁₋₄)alkyle, R₃ est un atome d'hydrogène ou le radical hydroxy, ainsi que leurs sels d'addition aux acides pharmaceutiquement acceptables. Application en thérapeutique.

  式(I)的嘧啶基氨基哌啶衍生物 其中 X 代表 (CH₂)₂、CH = CH 或 CH₂-CO 自由基、 Y 代表基 CH = CH 或硫原子、 n 为 2、3 或 4、 R₁ 是氢原子或卤素原子、 R₂ 是氢原子或 (C₁₋₄)烷基、 R₃ 是氢原子或羟基、 以及它们与药学上可接受的酸的加成盐。 治疗应用。