索非那新杂质K | 59653-40-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 中文名称: 索非那新杂质K
• 英文名称: R-aceclidine
• 英文别名: (+)-Aceclidine；[(3R)-1-azabicyclo[2.2.2]octan-3-yl] acetate
• CAS: 59653-40-6
• 化学式: C₉H₁₅NO₂
• 分子量: 169.224
• InChiKey: WRJPSSPFHGNBMG-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  索非那新杂质K 在 sodium hydroxide 作用下， 反应 1.0h， 以80%的产率得到(R)-(-)-3-奎宁醇
  参考文献：
  名称：

  Synthesis of (R) and (S)-3-Aminoquinuclidine from 3-Quinuclidinone and (S) and (R)-1-Phenethylamine

  摘要：

  The synthesis of (R) and (S)-3-amino quinuclidine, an important building block for the synthesis of chiral 5-HT3 serotonin receptor antagonists, is described. The key reaction is the reduction by NaBH4 of the imine prepared from the 3-quinuclidinone and chiral (S) or (R)-1-phenethylamine.

  DOI：

  10.1080/00397919208021320
• 作为产物：
  描述：

  乙酰克里定 生成 索非那新杂质K
  参考文献：
  名称：

  Synthesis of (R) and (S)-3-Aminoquinuclidine from 3-Quinuclidinone and (S) and (R)-1-Phenethylamine

  摘要：

  The synthesis of (R) and (S)-3-amino quinuclidine, an important building block for the synthesis of chiral 5-HT3 serotonin receptor antagonists, is described. The key reaction is the reduction by NaBH4 of the imine prepared from the 3-quinuclidinone and chiral (S) or (R)-1-phenethylamine.

  DOI：

  10.1080/00397919208021320
• 作为试剂：
  描述：

  在 索非那新杂质K 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以67%的产率得到1,3-二苯丙烷
  参考文献：
  名称：

  3-Acetoxyquinuclidine as Catalyst in Electron Donor–Acceptor Complex-Mediated Reactions Triggered by Visible Light

  摘要：

  3-Acetoxyquinuclidine was found to act as a catalytic electron donor species in a variety of electron donor-acceptor complex-mediated reactions. Only substoichiometric amounts (10-25 mol %) were needed to trigger the desired reaction. The outcome could be tuned by selecting the nature of the formed radical to perform amino and hydro-decarboxylation, dimerization, and cyclization reactions. Importantly, no external additives were needed in this reaction.

  DOI：

  10.1021/acscatal.9b01039

文献信息

• Process for the Preparation of Solifenacin and Salts Thereof
  申请人：Bessa Bellunt Jordi

  公开号：US20140228575A1

  公开（公告）日：2014-08-14

  The invention provides a new process for the preparation of solifenacin or a pharmaceutically acceptable acid addition salt thereof, comprising reacting (R)-quinuclidin-3-yl phenethylcarbamate with benzaldehyde in the presence of an acid to obtain a diasteroisomeric mixture (S,R)—((R)-quinuclidin-3-yl) 1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate of formula (IV) which can be resolved and the solifenacin or a pharmaceutically acceptable acid addition salt thereof recovered. The invention also provides the new key intermediate (R)-quinuclidin-3-yl phenethylcarbamate involved in the process. Further the invention provides a method for the transformation of (R)—((R)-quinuclidin-3-yl) 1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate into a diasteroisomeric mixture (S,R)—((R)-quinuclidin-3-yl) 1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate.

  该发明提供了一种制备索利那辛或其药用可接受的酸盐的新工艺，包括在酸的存在下将(R)-喹诺啡啶-3-基苯乙基氨基甲酸酯与苯甲醛反应，以获得一个立体异构混合物(S,R)-((R)-喹诺啡啶-3-基) 1-苯基-3,4-二氢异喹啉-2(1H)-羧酸酯的公式(IV)，该混合物可以被分离，并可回收索利那辛或其药用可接受的酸盐。该发明还提供了参与该工艺的新关键中间体(R)-喹诺啡啶-3-基苯乙基氨基甲酸酯。此外，该发明提供了一种将(R)-((R)-喹诺啡啶-3-基) 1-苯基-3,4-二氢异喹啉-2(1H)-羧酸酯转化为一个立体异构混合物(S,R)-((R)-喹诺啡啶-3-基) 1-苯基-3,4-二氢异喹啉-2(1H)-羧酸酯的方法。
• [EN] IMPROVED PROCESS FOR ACYL TRANSFER REACTIONS<br/>[FR] PROCÉDÉ AMÉLIORÉ POUR RÉACTIONS DE TRANSFERT D'ACYLE
  申请人：K H S PHARMA HOLDING GMBH

  公开号：WO2014140318A1

  公开（公告）日：2014-09-18

  The present invention relates to a novel process for the preparation of esters like Aclidinium, Atropin, Glycopyrroniunn, Tiotropium, Trospium and their respective precursors and derivatives, based on direct acyl transfer reactions.

  本发明涉及一种新颖的制备类似Aclidinium、Atropin、Glycopyrroniunn、Tiotropium、Trospium及其各自的前体和衍生物的酯类的过程，基于直接酰基转移反应。
• Process for preparing solifenacin
  申请人：Perlman Nurit

  公开号：US20070173528A1

  公开（公告）日：2007-07-26

  Provided are new intermediates of solifenacin and methods for their preparation, as well as methods of preparing solifenacin and solifenacin succinate.

  提供了索利那新中间体的制备方法，以及制备索利那新和索利那新琥珀酸盐的方法。
• Boronic acid adducts of rhenium dioxime and technetium-99M dioxime complexes containing a biochemically active group
  申请人：BRACCO INTERNATIONAL B.V.

  公开号：EP0441491A1

  公开（公告）日：1991-08-14

  Boronic acid adducts of technetium-99m and radioactive rhenium dioxime complexes, each of which include biochemically active groups, are useful as diagnostic and therapeutic agents, respectively.

  锝-99m 的硼酸加合物和放射性二氧化铼络合物都含有生化活性基团，可分别用作诊断和治疗药物。
• SCREENING METHOD
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP3627152A1

  公开（公告）日：2020-03-25

  The present invention provides a useful and efficient screening method for finding a cholinergic muscarinic M1 receptor positive allosteric modulator (M1PAM) with reduced cholinergic side effects. The present invention also provides a method for treating Alzheimer's disease and the like, a method for reducing cholinergic side effects, and the like which use M1PAM selected by the screening method and having a low α value, or the M1PAM and an acetylcholinesterase inhibitor.

  本发明提供了一种有用且高效的筛选方法，用于寻找具有降低胆碱能副作用的胆碱能毒蕈碱 M1 受体正性异位调节剂（M1PAM）。本发明还提供了一种治疗阿尔茨海默病等疾病的方法、一种减少胆碱能副作用的方法等，这些方法使用了通过筛选方法选出的具有低α值的M1PAM，或M1PAM和乙酰胆碱酯酶抑制剂。