(S)-1,2,3,4-Tetrahydro-1-phenylisoquinoline (2S,3S)-2,3-dihydroxybutanedioate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (S)-1,2,3,4-Tetrahydro-1-phenylisoquinoline (2S,3S)-2,3-dihydroxybutanedioate
• 英文别名: 2,3-dihydroxybutanedioic acid;1-phenyl-1,2,3,4-tetrahydroisoquinoline
• 化学式: C19H21NO6
• 分子量: 359.4
• InChiKey: SZEOPQAHUUEDMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  127
• 氢给体数：
  5
• 氢受体数：
  7

文献信息

• [EN] PROCESSES FOR THE PREPARATION OF SOLIFENACIN OR A SALT THEREOF<br/>[FR] PROCÉDÉS DE PRÉPARATION DE SOLIFÉNACINE OU D'UN DE SES SELS
  申请人：CADILA HEALTHCARE LTD

  公开号：WO2011048607A1

  公开（公告）日：2011-04-28

  The present invention describes recovery and racemization of (1R)-Phenyl- 1,2,3,4-tetrahydroisoquinoline of compound of formula (III) to obtain racemic 1- phenyl-1, 2,3,4-tetrahydroisoquinoline of compound of formula (I) and its further resolution to get ( IS)-1-phenyl-1, 2, 3, 4-tetrahydroisoquinoline (intermediate B) in high chemical and chiral purity, which is the key intermediate for the preparation of (3R)-azabicyclo[2.2.2]oct-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)- carboxylate.

  本发明描述了将化合物的(1R)-苯基-1,2,3,4-四氢异喹啉（III式化合物）进行回收和外消旋，以获得光学异构体1-苯基-1,2,3,4-四氢异喹啉（I式化合物），并进一步对其进行分离，得到高化学和手性纯度的(1S)-1-苯基-1,2,3,4-四氢异喹啉（中间体B），这是制备(3R)-氮杂双环[2.2.2]辛-3-基(1S)-1-苯基-3,4-二氢异喹啉-2-(1H)-羧酸酯的关键中间体。
• Processes for optical resolution of 1-phenyl-1,2,3,4-tetrahydroisoquinoline
  申请人：Perlman Nurit

  公开号：US20080091023A1

  公开（公告）日：2008-04-17

  Optically pure 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline tartrate is prepared. The 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline tartrate is particularly useful for preparing solifenacin succinate.

  制备了光学纯的1(S)-苯基-1,2,3,4-四氢异喹啉酒石酸盐。这种1(S)-苯基-1,2,3,4-四氢异喹啉酒石酸盐特别适用于制备索利那辛琥酸盐。
• [EN] PROCESS FOR THE PREPARATION OF SOLIFENACIN AND SOLIFENACIN SUCCINATE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE SOLIFÉNACINE ET DE SUCCINATE DE SOLIFÉNACINE
  申请人：ZAKLADY FARMACEUTYCZNE POLPHARMA SA

  公开号：WO2011086003A1

  公开（公告）日：2011-07-21

  A process for the preparation of solifenacin wherein all the reaction steps, starting from (i) release of (S) -I -phenyl- 1, 2,3, 4 - tetrahydroisoquinoline from its diastereoisomeric salt with D- (-) - tartaric acid, (ii) conversion of (S) - 1 -phenyl - 1, 2, 3, 4 - tetrahydroisoquinoline into 1 - (5) -phenyl - 1, 2, 3, 4 - tetrahydroisoquinolinecarbonyl chloride in the reaction with triphosgene in the presence of pyridine to (iii) the reaction between 1- (5) -phenyl - 1, 2, 3, 4 - tetrahydroisoquinolinecarbonyl chloride and 3- (S) - quinuclidinol in the presence of sodium hydride are carried out without the isolation of intermediates in solid form and the solvents used for the reactions are aprotic solvent. Resulting solifenacin in the free base form is converted into the corresponding succinic acid salt using methods known in the art.

  一种用于制备索利那辛的过程，其中所有的反应步骤，从（i）从其与D-(-)-酒石酸的非对映异构盐中释放（S）-I-苯基-1,2,3,4-四氢异喹啉开始，（ii）将（S）-1-苯基-1,2,3,4-四氢异喹啉转化为1-(5)-苯基-1,2,3,4-四氢异喹啉羰氯在三氯甲烷存在下与三氯甲烷反应生成1-(5)-苯基-1,2,3,4-四氢异喹啉羰氯，（iii）在氢化钠存在下1-(5)-苯基-1,2,3,4-四氢异喹啉羰氯与3-(S)-喹啉醇之间的反应均在无需固体中间体隔离的情况下进行，用于反应的溶剂为无极性溶剂。得到的自由碱形式的索利那辛通过艺术中已知的方法转化为相应的琥珀酸盐。
• PROCESSES FOR OPTICAL RESOLUTION OF 1-PHENYL-1,2,3,4-TETRAHYDROISOQUINOLINE
  申请人：Teva Pharmaceutical Industries Ltd.

  公开号：EP1922308A2

  公开（公告）日：2008-05-21
• Polymorphs of solifenacin intermediate
  申请人：Koltai Tamas

  公开号：US20080114029A1

  公开（公告）日：2008-05-15

  Polymorphic forms of 1(S)-phenyl-1,2,3,4-tetrahydroisoquinoline have been prepared and characterized. These polymorphic forms are particularly useful for preparing solifenacin salts.