(-)-1-(2-iodophenyl)-1,2,3,4-tetrahydroisoquinoline | 1448701-79-8

• 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: (-)-1-(2-iodophenyl)-1,2,3,4-tetrahydroisoquinoline
• 英文别名: (1S)-1-(2-iodophenyl)-1,2,3,4-tetrahydroisoquinoline
• CAS: 1448701-79-8
• 化学式: C₁₅H₁₄IN
• 分子量: 335.187
• InChiKey: GRDOSFGFNXZBKH-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  2-苯乙胺 在 [N-[(1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-methylbenzenesulfonamidato-κN]chloro[(1,2,3,4,5,6-η)-1,3,5-trimethylbenzene]ruthenium 、 甲酸 、 三氟甲磺酸酐 、 三乙胺 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 40.25h， 生成 (-)-1-(2-iodophenyl)-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Ru催化不对称转移氢化反应对映选择性合成1-芳基取代的四氢异喹啉

  摘要：

  使用 [RuIICl(η6-苯)TsDPEN] 配合物与 5:2 HCOOH-Et3N 共沸混合物作为氢源，方便且通用地对各种 1-芳基-3,4-二氢异喹啉衍生物进行不对称转移氢化已开发。在温和的反应条件下，所描述的催化转化确保了获得相应有价值的手性 1-芳基四氢异喹啉单元的实际合成途径，该单元具有高原子经济性、广泛的底物范围、高分离产率（高达 97%）和良好的对映选择性（高达99% ee)。发现反应的立体化学结果受催化剂结构和底物上存在的取代基的强烈影响。

  DOI：

  10.1002/ejoc.201500951

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 PREPARATION OF SOLIFENACIN AND/OR THE PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF OF HIGH PHARMACEUTICAL PURITY<br/>[FR] PROCEDE DE PREPARATION DE SOLIFENACINE ET/OU DE SES SELS PHARMACEUTIQUEMENT ACCEPTABLES DE HAUTE PURETE PHARMACEUTIQUE
  申请人：ZAKLADY FARM POLPHARMA SA

  公开号：WO2009142522A1

  公开（公告）日：2009-11-26

  A process for the preparation of solifenacin and/or the pharmaceutically acceptable salts thereof of high pharmaceutical purity is characterized in that 3-(R)-quinuclidinoloxy anion generated in situ from 3-(R)-quinuclidinol in a presence of strong base in polar organic solvent is subject to acylation with (S)-1 -phenyl-1,2,3, 4-tetrahydroisoquinolinecarbonyl chloride of chemical purity at least 98%, while maintaining constant anion excess in a reaction mixture, and after reaction completion solifenacin base is optionally transformed into solifenacin salt according to standard procedures. (S)-1-Phenyl-1,2,3,4-tetrahydroisoquinolinecarbonyl chloride of chemical purity at least 98% is obtained in a reaction of (S)-1-phenyl-1,2,3, 4- tetrahydroisoquinoline and molar excess of phosgene in a presence of tertiary aromatic amine in aromatic hydrocarbon, and isolated in a crystalline form.

  一种制备高纯度药物溶剂那非和/或其药用可接受盐的方法，其特征在于在极性有机溶剂中，在强碱的存在下，由3-(R)-喹诺酮醇生成的3-(R)-喹诺酮氧负离子在反应混合物中保持恒定的过量阴离子的情况下，与至少98%化学纯度的(S)-1-苯基-1,2,3,4-四氢异喹啉羰基氯化物发生酰基化反应，反应完成后，溶剂那非碱可选择地按标准程序转化为溶剂那非盐。至少98%化学纯度的(S)-1-苯基-1,2,3,4-四氢异喹啉羰基氯化物是通过(S)-1-苯基-1,2,3,4-四氢异喹啉和过量的光气在芳香烃的存在下，以及在结晶形式中分离。
• [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。
• Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of 1-Aryl-Substituted Dihydroisoquinolines: Access to Valuable Chiral 1-Aryl-Tetrahydroisoquinoline Scaffolds
  作者：Zi Wu、Marc Perez、Michelangelo Scalone、Tahar Ayad、Virginie Ratovelomanana-Vidal

  DOI：10.1002/anie.201301134

  日期：2013.4.26

  Give me an H! Give me another H! The first general and highly enantioselective Ru‐catalyzed transfer hydrogenation of a wide range of 1‐aryl‐substituted 1,2,3,4‐dihydroisoquinolines is described. This atom‐economic reaction proceeds under mild conditions, allowing rapid access to the corresponding biologically relevant 1‐aryl‐tetrahydroisoquinoline derivatives, in high yields and enantioselectivities

  给我一个H！再给我一个H！描述了第一个普通的和高对映选择性的Ru催化的广泛的1-芳基取代的1,2,3,4-二氢异喹啉的转移加氢反应。这种原子经济反应在温和的条件下进行，可以快速获得相应的生物学相关的1-芳基-四氢异喹啉衍生物，且收率高，对映选择性高达99％。
• [EN] PROCESS FOR PREPARATION OF ENANTIOMERICALLY PURE (S)-1-PHENYI-1,2,3,4- TETRAHYDROISOQUINOLINE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE (S)-1-PHÉNYL-1,2,3,4-TETRAHYDROISOQUINOLÉINE ENANTIOMÉRIQUEMENT PURE
  申请人：ZAKLADY FARM POLPHARMA SA

  公开号：WO2009142521A1

  公开（公告）日：2009-11-26

  Process for preparation of (S)-1 -phenyl-1, 2,3, 4-tetrahydroisoquinoline is characterized in that 1-phenyl-1,2,3, 4-tetrahydroisoquinoline is reacted with D-(-)- tartaric acid in a solvent system consisting of methanol and water, preferably at 3.3:1 to 1 :1 volume ratio, the crystallization mixture is left for crystallization and (S)-1-phenyl-1,2,3, 4-tetrahydroisoquinoline is released from obtained crystalline diastereoisomeric salt according to standard procedures. (S)-1-Phenyl- 1,2,3, 4-tetrahydroisoquinoline is the intermediate in enantiomeric synthesis of solifenacin.

  制备（S）-1-苯基-1,2,3,4-四氢异喹啉的过程特征在于将1-苯基-1,2,3,4-四氢异喹啉与D-（-）-酒石酸在甲醇和水的溶剂体系中反应，最好在3.3:1至1:1的体积比下，结晶混合物留置结晶，（S）-1-苯基-1,2,3,4-四氢异喹啉从获得的晶体对映异构盐中按照标准程序释放。 （S）-1-苯基-1,2,3,4-四氢异喹啉是索利费南对映体合成中的中间体。