索利那新-索非那新杂质 | 732228-02-3

• 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: 索利那新-索非那新杂质
• 英文名称: (1S)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylic acid (3S)-1-azabicyclo[2.2.2]oct-3-yl ester
• 英文别名: Solifenacin Succinate EP Impurity H；[(3S)-1-azabicyclo[2.2.2]octan-3-yl] (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate
• CAS: 732228-02-3
• 化学式: C₂₃H₂₆N₂O₂
• 分子量: 362.472
• InChiKey: FBOUYBDGKBSUES-YADHBBJMSA-N

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：

  索利那新-索非那新杂质 、 (1R,3R)-索利那新杂质2 、 L-酒石酸 、 索非那新 以 甲醇 、 异丙醇 为溶剂， 以79%的产率得到酒石酸索利那新
  参考文献：
  名称：

  WO2008/77357

  摘要：

  公开号：
• 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 索利那新-索非那新杂质
  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] NOVEL PROCESS FOR THE PREPARATION OF SOLIFENACIN SUCCINATE<br/>[FR] NOUVEAU PROCÉDÉ POUR LA PRÉPARATION DE SUCCINATE DE SOLIFÉNACINE
  申请人：AUROBINDO PHARMA LTD

  公开号：WO2012001481A1

  公开（公告）日：2012-01-05

  The present invention relates to a process for the preparation of Solifenacin succinate by condensing a compound of formula (IVb) with (RS)-3-quinuclidinol, wherein, R represents methyl, ethyl, isopropyl; to produce a diastereomeric mixture of ( 1S)-3,4-dihydro- 1 -phenyl-2( 1 H)-isoquinolinecarboxylic acid (3RS)- 1 - azabicyclo[2.2.2]oct-3-yl ester, which is treated with succinic acid in a solvent or mixture of solvents to produce optically pure Solifenacin succinate, Formula (X).

  本发明涉及一种通过将式（IVb）的化合物与（RS）-3-喹诺啉醇（其中，R代表甲基、乙基、异丙基）缩合制备索利那非琥酸盐的方法，以产生（1S）-3,4-二氢-1-苯基-2(1H)-异喹啉羧酸（3RS）-1-氮杂双环[2.2.2]辛-3-基酯的对映体混合物，该混合物与琥珀酸在溶剂或溶剂混合物中反应，制备光学纯的索利那非琥酸盐，化学式（X）。
• NOVEL PROCESS FOR THE PREPARATION OF SOLIFENACIN SUCCINATE
  申请人：Kamat Anand Gopalkrishna

  公开号：US20130123502A1

  公开（公告）日：2013-05-16

  The present invention relates to a process for the preparation of Solifenacin succinate by condensing a compound of formula (IVb) with (RS)-3-quinuclidinol, wherein, R represents methyl, ethyl, isopropyl; to produce a diastereomeric mixture of (1S)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylic acid (3RS)-1-azabicyclo[2.2.2]oct-3-yl ester, which is treated with succinic acid in a solvent or mixture of solvents to produce optically pure Solifenacin succinate, Formula (X).

  这项发明涉及一种通过将式（IVb）化合物与（RS）-3-喹诺啉醇缩合来制备索利那辛琥酸盐的方法，其中，R代表甲基、乙基、异丙基；以产生（1S）-3,4-二氢-1-苯基-2(1H)-异喹啉羧酸（3RS）-1-氮杂双环[2.2.2]辛-3-基酯的对映体混合物，该混合物与琥珀酸在溶剂或溶剂混合物中反应，以产生光学纯的索利那辛琥酸盐，化学式（X）。
• 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。
• PROCESS FOR PREPARING SOLIFENACIN AND ITS SALTS
  申请人：Mathad Vijayavitthal Thippannachar

  公开号：US20090326230A1

  公开（公告）日：2009-12-31

  The present invention relates to solifenacin in solid form and a process for its preparation and to a process for the preparation of (1S)-1-Phenyl-1,2,3,4-tetrahydro-isoquinoline, a key intermediate in the synthesis of solifenacin and its salts.

  本发明涉及固体形式的索利那新及其制备方法，以及制备（1S）-1-苯基-1,2,3,4-四氢异喹啉的方法，该中间体是合成索利那新及其盐的关键步骤。