(1R,3S)-索利那新杂质2 | 774517-20-3

• 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: (1R,3S)-索利那新杂质2
• 英文名称: (3S)-1-azabicyclo[2.2.2]oct-3-yl (1R)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylate
• 英文别名: solifenacin；[(3S)-1-azabicyclo[2.2.2]octan-3-yl] (1R)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate
• CAS: 774517-20-3
• 化学式: C₂₃H₂₆N₂O₂
• 分子量: 362.472
• InChiKey: FBOUYBDGKBSUES-FGZHOGPDSA-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,3S)-索利那新杂质2 、 索非那新 在 盐酸 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 生成 (1S,3'S)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monohydrochloride 、 索利那新盐酸盐 、 (1R,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monohydrochloride 、 、 (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline hydrochloride
  参考文献：
  名称：

  EP1714965

  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 (1R,3S)-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

• METHOD FOR THE PREPARATION OF SOLIFENACIN AND INTERMEDIATE THEREOF
  申请人：Mathad Vijayvitthal Thippannachar

  公开号：US20110319621A1

  公开（公告）日：2011-12-29

  A method for the preparation of solifenacin by reacting quinuclidin-3-ol and bis(aryl) carbonate to form (3R)-1-azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate of formula (IVa); and treating (3R)-1-azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate of formula (IVa) with (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline of formula (V) in an inert atmosphere to form a Solifenacin base, which is converted into its pharmaceutically acceptable salts. The invention also provides a compound, (3R)-1-azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate of formula (IVa), which is used as an intermediate for the preparation of Solifenacin base and a process for the preparation thereof.

  一种制备索利那新的方法，通过反应三氢喹啉醇和双(芳基)碳酸酯生成公式(IVa)的(3R)-1-氮杂双环[2.2.2]辛-3-基4-芳基碳酸酯; 并在惰性气氛下处理公式(IVa)的(3R)-1-氮杂双环[2.2.2]辛-3-基4-芳基碳酸酯和公式(V)的(1S)-1-苯基-1,2,3,4-四氢异喹啉，形成索利那新碱，再转化为其药学上可接受的盐。本发明还提供一种化合物，公式为(IVa)的(3R)-1-氮杂双环[2.2.2]辛-3-基4-芳基碳酸酯，用作制备索利那新碱的中间体以及其制备方法。
• Method for producing solifenacin or salts thereof
  申请人：Inakoshi Masatoshi

  公开号：US20070185329A1

  公开（公告）日：2007-08-09

  There is provided a novel method for producing solifenacin or a salt thereof which is useful as a medicine, particularly a therapeutic agent and/or a preventive agent for a urinary organ system disease such as pollakiuria or urinary incontinence. Illustratively, there are provided (1) a method for producing solifenacin in which 2-(1H-imidazolylcarbonyl)-1-phenyltetrahydroisoquinoline is used as the starting material, (2) a method for producing solifenacin succinate in which (1RS)-phenyltetrahydroisoquinoline-carboxylic acid quinuclidinyl ester is used as the starting material, (3) a method for producing solifenacin in which a lower alkyl quinuclidinyl carbonate is used as the starting material and (4) a method for producing solifenacin in which phenyltetrahydroisoquinoline-carboxylic acid secondary lower alkyl or tertiary lower alkyl ester is used as the starting material and allowed to react with an alkali metal lower alkoxide.

  提供了一种新的制备索利费南或其盐的方法，该方法可用作药物，特别是用于治疗和/或预防尿生殖器官疾病，如尿频或尿失禁的治疗剂和/或预防剂。例如，提供了以下四种方法：（1）使用2-（1H-咪唑基）-1-苯基四氢异喹啉作为起始材料制备索利费南的方法；（2）使用（1RS）-苯基四氢异喹啉-羧酸奎尼克啶酯作为起始材料制备索利费南琥珀酸盐的方法；（3）使用较低烷基奎尼库啶碳酸酯作为起始材料制备索利费南的方法；（4）使用苯基四氢异喹啉-羧酸次级较低烷基或三级较低烷基酯作为起始材料，并与碱金属较低烷氧化物反应制备索利费南的方法。
• Solifenacin Succinate-Containing Composition
  申请人：Ishii Yusuke

  公开号：US20080287680A1

  公开（公告）日：2008-11-20

  A solifenacin succinate-containing composition with less impurities which can be used as a bulk for pharmaceutical is provided. The solifenacin succinate-containing composition of the present invention has a reduced content of especially its optical isomers in comparison with the known compositions containing an acid addition salt of solifenacin, so that it can be used for production of a therapeutic agent containing solifenacin succinate. In addition, the above-described solifenacin succinate-containing composition can be easily produced in accordance with the production method of the present invention.

  提供了一种含有较少杂质的索利费南琥酸盐组成物，可用作制药原料。本发明的索利费南琥酸盐组成物与含有索利费南酸盐的已知组成物相比，其光学异构体的含量降低，因此可用于生产含有索利费南琥酸盐的治疗剂。此外，上述索利费南琥酸盐组成物可以根据本发明的生产方法轻松制备。
• Efficient and single pot process for the preparation of enantiomerically pure solifenacin succinate, an antimuscarinic agent
  作者：Navnath C. Niphade、Kunal M. Jagtap、Anil C. Mali、Pavankumar V. Solanki、Madhukar N. Jachak、Vijayavitthal T. Mathad

  DOI：10.1007/s00706-011-0610-7

  日期：2011.11

  The development of an efficient and economic one-pot process, in which the configuration of the chiral centers of the starting materials is retained, for the preparation of highly pure solifenacin succinate, an antimuscarinic agent, is presented in this communication. The earlier reported processes suffer from the drawbacks of racemization and low yields due to the use of strong base, higher temperatures, and longer reaction times. The present work circumvents these issues by activating (3R)-quinuclidin-3-ol into a mixed active carbonate derivative by treating it with bis(4-nitrophenyl)carbonate. The subsequent reaction of the active carbonate with an enantiomerically pure amine without using any base at ambient temperature provided enantiomerically pure solifenacin with an overall yield of 90%.
• A NEW METHOD FOR THE PREPARATION OF SOLIFENACIN AND NEW INTERMEDIATE THEREOF
  申请人：Megafine Pharma (P) Ltd.

  公开号：EP2406257B1

  公开（公告）日：2019-08-07