(1R,3R)-索利那新杂质2 | 740780-79-4

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 中文名称: (1R,3R)-索利那新杂质2
• 英文名称: (R)-quinuclidin-3-yl (R)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate
• 英文别名: solifenacin；(3R)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylate；(-)-(3R)-quinuclidin-3-yl (1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate；(-)-(1R,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydro-isoquinoline-2-carboxylate；(R)-((R)-quinuclidin-3-yl) 1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate；Solifenacin Succinate EP Impurity G；[(3R)-1-azabicyclo[2.2.2]octan-3-yl] (1R)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate
• CAS: 740780-79-4
• 化学式: C₂₃H₂₆N₂O₂
• 分子量: 362.472
• InChiKey: FBOUYBDGKBSUES-FCHUYYIVSA-N

物化性质

• 沸点：
  505.5±50.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,3R)-索利那新杂质2 在 氢溴酸 作用下， 以 乙醇 、 异丙醚 、 水 为溶剂， 反应 18.0h， 生成 (-)-(3R)-quinuclidin-3-yl (1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate hydrobromide
  参考文献：
  名称：

  NOVEL SALTS OF QUINUCLIDINE DERIVATIVE

  摘要：

  提供了(-)-(3R)-喹硫脒-3-基(1R)-1-苯基-1,2,3,4-四氢异喹啉-2-羧酸盐，与以下酸之一选择的酸形成盐：(-)-(2S,3S)-酒石酸，(+)-(2S,3S)-二-O-苯甲酰酒石酸，(+)-(2S,3S)-二-O-(4-甲基苯甲酰)酒石酸，(-)-L-苯丙氨酸，苯磺酸，环己磺酸，氢溴酸，萘-2-磺酸，癸二酸，(+)-樟脑-10-磺酸，对甲苯磺酸，乙烷磺酸，甲烷磺酸和磷酸甲酯。该盐具有很少的吸湿性，不影响其作为药物或药物成分的使用，非常适用作为药物或药物成分。

  公开号：

  US20060205770A1
• 作为产物：
  描述：

  1-苯基-3,4-二氢异喹啉 在 sodium tetrahydroborate 、 sodium hydride 、 potassium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 60.0h， 生成 (1R,3R)-索利那新杂质2
  参考文献：
  名称：

  Synthesis and Antimuscarinic Properties of Quinuclidin-3-yl 1,2,3,4-Tetrahydroisoquinoline-2-carboxylate Derivatives as Novel Muscarinic Receptor Antagonists

  摘要：

  In the course of continuing efforts to develop potent and bladder-selective muscarinic M-3 receptor antagonists, quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives and related compounds were designed as conformationally restricted analogues of quinuclidin-3-yl benzhydrylcarbamate (8). Binding assays with rat muscarinic receptor subtypes revealed that the quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives showed high affinities for the M3 receptor, and selectivity for the M3 receptor over the M-2 receptor. Of these derivatives, (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monohydrochloride (9b) exhibited almost the same inhibitory activity against bladder contraction to that of oxybutynin (1), and more than 10-fold selectivity for bladder contraction versus salivary secretion, demonstrating that 9b may be useful for the treatment of symptoms associated with overactive bladder without having side effects such as dry mouth.

  DOI：

  10.1021/jm050099q

文献信息

• [EN] PROCESS FOR PREPARING CHEMICALLY AND CHIRALLY PURE SOLIFENACIN BASE AND ITS SALTS<br/>[FR] PROCÉDÉ DE PRÉPARATION D'UNE SOLIFÉNACINE BASE DE PURETÉ CHIMIQUE ET DE PURETÉ CHIRALE ET DE SES SELS
  申请人：CADILA HEALTHCARE LTD

  公开号：WO2009087664A1

  公开（公告）日：2009-07-16

  The present invention provides improved processes for preparing chemically and chirally pure Solifenacin base. The present invention also provides for a composition comprising of a salt of Solifenacin having at least 98 % purity. The present invention also disclose certain new salts of Solifenacin as well as well as new polymorphic forms of Solifenacin hydrochloride and Solifenacin oxalate, in pure form.

  本发明提供了改进的制备化学纯和对映纯索利那辛碱的方法。本发明还提供了一种含有至少98%纯度的索利那辛盐的组合物。本发明还披露了索利那辛的某些新盐以及索利那辛盐酸盐和索利那辛草酸盐的新多形态，均为纯形式。
• [EN] PROCESS FOR THE PREPARATION OF SOLIFENACIN AND SALTS THEREOF<br/>[FR] PROCÉDÉ D'ÉLABORATION DE SOLIFÉNACINE ET DE SELS DE SOLIFÉNACINE
  申请人：ISOCHEM SA

  公开号：WO2012175119A1

  公开（公告）日：2012-12-27

  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(1 H)-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(1 H)-carboxylate into a diasteroisomeric mixture (S,R)-((R)- quinuclidin-3-yl) 1 -phenyl-3,4-dihydroisoquinoline-2(1 H)-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)-喹诺啉-3-基苯乙基氨甲酸酯与苯甲醛反应，以获得一个对映异构体混合物(S,R)-((R)-喹诺啉-3-基) 1-苯基-3,4-二氢异喹啉-2(1 H)-羧酸酯的公式(IV)，该混合物可以被分离，然后可以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)-喹诺啉-3-基苯乙基氨甲酸酯。此外，该发明提供了一种将(R)-((R)-喹诺啉-3-基) 1-苯基-3,4-二氢异喹啉-2(1 H)-羧酸酯转化为一个对映异构体混合物(S,R)-((R)-喹诺啉-3-基) 1-苯基-3,4-二氢异喹啉-2(1 H)-羧酸酯的方法。
• 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。
• METHOD FOR THE PREPARATION OF SOLIFENACIN
  申请人：Jirman Josef

  公开号：US20100145055A1

  公开（公告）日：2010-06-10

  A method of preparing (1S)-(3R)-1-azabicyclo[2.2.2]oct-3-yl 3,4-dihydro-1-phenyl-2(1H)-isoquinoline carboxylate (solifenacin) or its pharmaceutically acceptable salts with high optic purity, wherein the crude solifenacin base is transformed to the hydrogen tartrate, which is then optionally transformed to another pharmaceutically acceptable salt or the base of solifenacin. A crystalline salt of solifenacin hydrogen tartrate.

  一种制备（1S）-（3R）-1-azabicyclo[2.2.2]辛-3-基 3,4-二氢-1-苯基-2(1H)-异喹啉羧酸酯（索利那辛）或其具有高光学纯度的药用盐的方法，其中粗索利那辛碱转化为酒石酸氢盐，然后可选择将其转化为另一种药用盐或索利那辛碱。索利那辛酒石酸氢盐的结晶盐。
• PROCESS FOR THE PREPARATION OF SOLIFENACIN
  申请人：Jirman Josef

  公开号：US20090203914A1

  公开（公告）日：2009-08-13

  A process for the preparation of (1S)-QR)-I -azabicyclo[2.2.2.]oct-3-yl 3,4-dihydro-1-phenyl- 2(1H)-isoquino-line carboxylate by reacting (1S)-alkyl 1-phenyl-1,2,3,4-tetrahydro-2-isoquinoline carboxylate with 3-(R)-quinuclidol in an inert solvent, where a primary alkyl ester of the carboxylate whose alkyl length is C 1 -C 4 is used and the reaction is catalyzed by a non-nu-cleophilic base.

  使用一种过程制备(1S)-QR)-I -azabicyclo[2.2.2.]oct-3-yl 3,4-二氢-1-苯基-2(1H)-异喹啉羧酸酯，方法是将(1S)-烷基-1-苯基-1,2,3,4-四氢-2-异喹啉羧酸酯与3-(R)-喹啉醇在惰性溶剂中反应，其中使用碳链长度为C1-C4的羧酸酯的一级烷基酯，反应由非亲核碱催化。