N-苄基溴化金鸡纳碱 | 118089-84-2

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 金鸡纳生物碱
• 中文名称: N-苄基溴化金鸡纳碱
• 英文名称: (2S,4S,5R)-1-benzyl-2-((R)-hydroxy(quinolin-4-yl)methyl)-5-vinylquinuclidin-1-ium bromide
• 英文别名: N-benzylcinchonidinium bromide；N-benzyl cinchonidine bromide；N-benzylcinchonidinium；quinine；N-benzyl cinchonidinium bromide；N-benzylcinchonidium bromide；(R)-[(2S,4S,5R)-1-benzyl-5-ethenyl-1-azoniabicyclo[2.2.2]octan-2-yl]-quinolin-4-ylmethanol;bromide
• CAS: 118089-84-2
• 化学式: Br*C₂₆H₂₉N₂O
• 分子量: 465.433
• InChiKey: UUVFTQCFSNVLGV-IOPLZPHGSA-M

物化性质

• 熔点：
  190 °C (dec.)(lit.)
• 稳定性/保质期：
  如果按照规格使用和储存，则不会分解，也未有已知的危险反应。应避免与强氧化物接触。

计算性质

• 辛醇/水分配系数(LogP)：
  1.88
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 安全说明：
  S26,S36
• 储存条件：
  保持贮藏器密封，并将其存放在阴凉、干燥处。确保工作间有良好的通风或排气装置。

反应信息

• 作为反应物：
  描述：

  N-苄基溴化金鸡纳碱 在 copper(l) iodide 、 三乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 48.0h， 生成 (2S,4S,5R)-1-benzyl-2-((R)-((1-decyl-1H-1,2,3-triazol-4-yl)methoxy)(quinolin-4-yl)methyl)-5-vinylquinuclidin-1-ium chloride
  参考文献：
  名称：

  One-Pot Synthesis of Au@SiO₂ Catalysts: A Click Chemistry Approach

  摘要：

  Using the copper-catalyzed azidealkyne cycloaddition click reaction, a library of triazole amphiphiles with a variety of functional polar heads and hydrophobic or superhydrophobic tails was synthesized. The amphiphiles were evaluated for their ability to stabilize small Au nanoparticles, and, at the same time, serve as templates for nanocasting porous SiO2. One of the Au@SiO2 materials thus prepared was found to be a highly active catalyst for the Au nanoparticle-catalyzed regioselective hydroamination of alkynes.

  DOI：

  10.1021/co5000932
• 作为产物：
  描述：

  溴甲苯 、 辛可尼丁 以 乙腈 为溶剂， 生成 N-苄基溴化金鸡纳碱
  参考文献：
  名称：

  Organocatalytic Activity of Cinchona Alkaloids: Which Nitrogen Is More Nucleophilic?

  摘要：

  The cinchona alkaloids 1a-d react selectively at the quinuclidine ring with benzyl bromide it and at the quinoline ring with benzhydrylium ions (diarylcarbenium ions). The kinetics of these reactions have been determined photometrically or conductimetrically and are compared with analogous reactions of quinuclidine and quinoline derivatives. Quantum chemical calculations [MP2/6-31 + G(2d p)// B3LYP/6-31G(d)] show that the products obtained by attack at the quinuclidine ring (N-sp3) of quinine are thermodynamically more stable when small alkylating agents (primary alkyl) are used, while the products arising from attack at the quinoline ring (N-sp2) are more stable for bulkier electrophiles (Ar2CH). In some cases, rate and equilibrium constants for their reactions with berizhydrylium ions could be determined. These data gave access to the Marcus intrinsic barriers, which are approximately 20 U mol(-1) lower for attack at the N-sp3-center than at the N-sp2-center.

  DOI：

  10.1021/jo901670w
• 作为试剂：
  描述：

  5-[(E)-丙-1-烯基]苯并[1,3]二氧杂环戊烯 在 N-溴代丁二酰亚胺(NBS) 、 水 、 N-苄基溴化金鸡纳碱 作用下， 以 二甲基亚砜 为溶剂， 反应 0.25h， 以48%的产率得到2-(benzo[d][1,3]dioxol-5-yl)propanal
  参考文献：
  名称：

  MICROWAVE INDUCED SINGLE STEP GREEN SYNTHESIS OF SOME NOVEL 2-ARYL ALDEHYDES AND THEIR ANALOGUES

  摘要：

  本发明提供了一种制备一些新型2-芳基和2,2-二芳基醛类及类似物的过程，这些中间体是商业上重要的非类固醇抗炎药物（包括萘普生、氟比洛芬等）和潜在的抗癌药物候选药物（包括苯斯他汀）的特权中间体，通过一种独特的单步合成方法利用易得的芳基烯烃底物以及环境友好的水相反应条件，如水和二甲基亚砜或二恶烷的混合物，以及试剂N-溴代琥珀酰亚胺、N-碘代琥珀酰亚胺、N-氯代琥珀酰亚胺和相转移催化剂（如溴化十六烷基三甲基铵、N-己基氯化铵）进行反应，反应时间从1分钟至30分钟不等，取决于微波或传统加热，无需使用昂贵的过渡金属催化剂或路易斯酸碱，收率在35-55%之间变化，取决于所使用的溶剂和底物。该方法提供了一种干净、方便的替代方案，可访问各种重要的药用2-芳基和2,2-二芳基醛基骨架，而不是采用传统的多步协议，这些多步协议使用昂贵和危险的过渡金属催化剂和路易斯酸碱。

  公开号：

  US20120041234A1

文献信息

• [EN] EX VIVO METHODS FOR PREDICTING AND CONFIRMING IN VIVO METABOLISM OF PHARMACEUTICALLY ACTIVE COMPOUNDS<br/>[FR] MÉTHODES EX VIVO PERMETTANT DE PRÉDIRE ET DE CONFIRMER LE MÉTABOLISME IN VIVO DE COMPOSÉS PHARMACEUTIQUEMENT ACTIFS
  申请人：EMPIRIKO CORP

  公开号：WO2015089089A1

  公开（公告）日：2015-06-18

  Methods and compositions for the catalytic oxidation of pharmaceutically active compounds, and more particularly to ex vivo methods for predicting in vivo metabolism of pharmaceutically active compounds, including predicting in vivo interaction between two or more pharmaceutically active compounds.

  用于催化氧化药用活性化合物的方法和组合物，更具体地用于预测药用活性化合物体外代谢的方法，包括预测两种或更多药用活性化合物之间的体内相互作用。
• [EN] PROCESS FOR THE PREPARATION OF GAMMA AMINO ACIDS AND INTERMEDIATES USED IN SAID PROCESS<br/>[FR] PROCÉDÉ DE PRÉPARATION DE ACIDES AMINÉS GAMMA ET INTERMÉDIAIRES UTILISÉS DANS CE PROCÉDÉ
  申请人：ROYAL COLLEGE OF SURGEONS IE

  公开号：WO2013076225A1

  公开（公告）日：2013-05-30

  The invention relates to the preparation of gamma amino acids of formula (I) and pharmaceutically acceptable salts, solvates and prodrugs thereof, and to intermediates used for their preparation. (formula I) wherein R1 is selected from an alkyl group, an alkenyl group, an alkynyl group and a cycloalkyl group, each of which may be optionally substituted and * denotes a chiral centre. In particular, the present invention provides an efficient synthesis of (S)-pregabalin which is suitable for carrying out on an industrial scale.

  该发明涉及制备公式(I)的γ-氨基酸及其药学上可接受的盐、溶剂合物和前药，以及用于其制备的中间体。(公式I)其中R1选自烷基、烯基、炔基和环烷基，每种基团均可选择性地被取代，*表示一个手性中心。特别是，本发明提供了(S)-普瑞巴林的高效合成方法，适用于工业规模生产。
• Enantioselective Hydrogenation of α,β-Unsaturated Carboxylic Acids over Cinchonidine Modified Palladium: Nature of Modifier–Reactant Interaction
  作者：K. Borszeky、T. Bürgi、Z. Zhaohui、T. Mallat、A. Baiker

  DOI：10.1006/jcat.1999.2584

  日期：1999.10

  The mechanism of enantiodifferentiation in the hydrogenation of alkenoic acids over cinchona-modified Pd has been investigated using the tiglic acid → 2-methyl-butanoic acid transformation as test reaction. Application of simple derivatives of cinchonidine, modified at the (C-9)–OH and/or the quinuclidine nitrogen, proved that both functional groups are involved in the enantiodiscriminating step. Addition

  以钛酸→2-甲基丁酸转化为测试反应，研究了金鸡纳修饰的Pd上链烯酸加氢中对映异构化的机理。应用在（C-9）-OH和/或喹核苷氮上修饰的辛可尼定的简单衍生物，证明这两个官能团均参与对映异构步骤。在氢化之前，将强碱（1,8-二氮杂双环[5.4.0]十一碳-7-烯，DBU）添加到叔丁酸中表明，一个辛可尼定分子与金属表面上的叔丁酸二聚体相互作用。从头算就证实了通过氢键稳定的，受能量支持的酸性二聚体-可可宁中间体的存在，该中间体涉及可可宁的OH和奎宁环氮。
• Process for producing optically active alpha-substituted cysteine or salt thereof, intermediate therefor, and process for producing the same
  申请人：Maruoka Keiji

  公开号：US20060069134A1

  公开（公告）日：2006-03-30

  The present invention provides a simple, practical, and industrially advantageous process for producing an optically active α-substituted cysteine or a salt thereof from inexpensive and readily available materials. The present invention provides a process for producing an optically active α-substituted cysteine or a salt thereof by converting a cysteine derivative into a thiazoline compound and subjecting the resulting thiazoline compound to a stereoselective substituent-introducing reaction catalyzed by an optically active quaternary ammonium salt, in particular, an axially asymmetric quaternary ammonium salt to produce an optically active thiazoline compound and then hydrolyzing the resulting thiazoline compound.

  本发明提供一种简单、实用且具有工业优势的工艺，从廉价且易得的材料中生产出光学活性的α-取代半胱氨酸或其盐。本发明提供了一种生产光学活性α-取代半胱氨酸或其盐的工艺，通过将半胱氨酸衍生物转化为噻唑环化合物，并将所得的噻唑环化合物在光学活性季铵盐的催化下进行立体选择性取代基引入反应，特别是在轴向不对称季铵盐的催化下，产生光学活性噻唑环化合物，然后水解所得的噻唑环化合物。
• PROCESS FOR THE PREPARATION OF GAMMA AMINO ACIDS AND INTERMEDIATES USED IN SAID PROCESS
  申请人：Royal College of Surgeons in Ireland

  公开号：US20140336412A1

  公开（公告）日：2014-11-13

  The invention relates to the preparation of gamma amino acids of formula (I) and pharmaceutically acceptable salts, solvates and prodrugs thereof, and to intermediates used for their preparation. (formula I) wherein R 1 is selected from an alkyl group, an alkenyl group, an alkynyl group and a cycloalkyl group, each of which may be optionally substituted and * denotes a chiral centre. In particular, the present invention provides an efficient synthesis of (S)-pregabalin which is suitable for carrying out on an industrial scale.

  本发明涉及制备公式(I)的γ-氨基酸及其药学上可接受的盐、溶剂化物和前药，以及用于它们制备的中间体。(公式I)其中R1选自烷基、烯基、炔基和环烷基，每个基团均可选择性地被取代，*表示手性中心。特别地，本发明提供了一种适用于工业规模的(S)-pregabalin的高效合成方法。