N-acetyl-1-(4-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline

• 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: N-acetyl-1-(4-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 1-[(1S)-1-(4-chlorophenyl)-6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl]ethanone
• 化学式: C₁₉H₂₀ClNO₃
• 分子量: 345.826
• InChiKey: KHIAPCKDMQGBOL-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-(3-(苄氧基)-4-甲氧基苯基)乙胺 在 盐酸 、 1,1’-bi-2-naphthol 、 palladium 10% on activated carbon 、 (R)-3,3′-bis(2,4,6-triisopropylphenyl)-BINOL-phosphoric acid 、 氢气 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 氯仿 、 甲苯 、 乙腈 为溶剂， 反应 24.25h， 生成 N-acetyl-1-(4-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Organocatalytic Enantioselective Pictet–Spengler Reactions for the Syntheses of 1-Substituted 1,2,3,4-Tetrahydroisoquinolines

  摘要：

  A series of 1-substituted 1,2,3,4-tetrahydroisoquinolines was prepared from N-(o-nitrophenylsulfenyl)phenylethylamines through BINOL-phosphoric acid [(R)-TRIP]-catalyzed asymmetric Pictet-Spengler reactions. The sulfenamide moiety is crucial for the rate and enantioselectivity of the iminium ion cyclization and the products are readily recrystallized to high enantiomeric purity. Using this methodology we synthesized the natural products (R)-crispine A, (R)-calycotomine and (R)-colchietine, the synthetic drug (R)-almorexant and the (S)-enantiomer of a biologically active (R)-AMPA-antagonist.

  DOI：

  10.1021/jo501099h

文献信息

• Josiphos-Type Binaphane Ligands for Iridium-Catalyzed Enantioselective Hydrogenation of 1-Aryl-Substituted Dihydroisoquinolines
  作者：Huifang Nie、Yupu Zhu、Xiaomu Hu、Zhao Wei、Lin Yao、Gang Zhou、Pingan Wang、Ru Jiang、Shengyong Zhang

  DOI：10.1021/acs.orglett.9b03251

  日期：2019.11.1

  displayed excellent enantioselectivity and good reactivity in the asymmetric hydrogenation of challenging 1-aryl-substituted dihydroisoquinoline substrates (full conversions, up to >99% ee, 4000 TON). The use of 40% HBr (aqueous solution) as an additive dramatically improved the asymmetric induction of these catalysts. This transformation provided a highly efficient and enantioselective access to chiral

  描述了一系列Josiphos型双苯甲醚配体的简便合成方法和有用的应用。这些手性二膦的铱络合物在具有挑战性的1-芳基取代的二氢异喹啉底物的不对称氢化中显示出出色的对映选择性和良好的反应性（完全转化，高达> 99％ee，4000 TON）。使用40％HBr（水溶液）作为添加剂可显着改善这些催化剂的不对称诱导。该转化提供了对手性1-芳基取代的四氢异喹啉的高效和对映选择性的途径，这在天然产物和生物活性分子中非常重要且常见。
• Dual Stereocontrol for Enantioselective Hydrogenation of Dihydroisoquinolines Induced by Tuning the Amount of <i>N</i> -Bromosuccinimide
  作者：Yue Ji、Jie Wang、Muwang Chen、Lei Shi、Yonggui Zhou

  DOI：10.1002/cjoc.201700634

  日期：2018.2

  An efficient dual stereocontrol in iridium‐catalyzed hydrogenation of 1‐substituted 3,4‐dihydroisoquinolines was realized by tuning the amount of N‐bromosuccinimide using chiral ligand of single configuration, providing both enantiomers of 1‐substituted 1,2,3,4‐tetrahydroisoquinolines with up to 89% ee (S) and 98% ee (R), respectively. Dual activation role of N‐bromosuccinimide is proposed to be responsible

  通过使用单一构型的手性配体调节N-溴代琥珀酰亚胺的量，提供了1-取代的1,2,3,4-四氢异喹啉，分别具有高达89％的ee（S）和98％的ee（R）。N-溴代琥珀酰亚胺的双重活化作用被认为是在两个氢化条件下逆转对映选择性的原因。
• Stereoselective Total Syntheses of Solifenacin and N-Acetyl-1-(4-chloro­phenyl)-6,7-dimethoxytetrahydroisoquinoline
  作者：B. Reddy、R. Babu、N. Reddy、B. Reddy

  DOI：10.1055/s-0034-1378515

  日期：——

  A highly stereoselective synthesis of 1-aryl-1,2,3,4-tetrahydroisoquinoline drugs such as solefinacin (muscarinic acetylcholine receptor antagonist) and N-acetyl-1-(4-chlorophenyl)-6,7-dimethoxytetrahydroisoquinoline (AMPA receptor antagonist) has been accomplished using (R)-tert-butanesulfinamide as a chiral source. Chiral tetrahydroisoquinolines have been prepared through the aryl Grignard addition to chiral N-sulfinylimines followed by haloamide cyclization.
• Synthesis, resolution, stereochemistry, and molecular modeling of (R)- and (S)-2-acetyl-1-(4′-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline AMPAR antagonists
  作者：Rosaria Gitto、Rita Ficarra、Rosanna Stancanelli、Marta Guardo、Laura De Luca、Maria Letizia Barreca、Benedetta Pagano、Archimede Rotondo、Giuseppe Bruno、Emilio Russo、Giovanbattista De Sarro、Alba Chimirri

  DOI：10.1016/j.bmc.2007.05.059

  日期：2007.8

  Recently we identified (R,S)-2-acetyl-1-(4'-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6) as a potent non-competitive AMPA receptor antagonist able to prevent epileptic seizures. We report here the optimized synthesis of compound 6, its resolution by chiral preparative HPLC, and the absolute configuration of (R)-enantiomer established by X-ray diffractometry. The biological tests of the single enantiomers revealed that higher anticonvulsant and antagonistic effects reside in (R)-enantiomer as also suggested by molecular modeling studies. (c) 2007 Elsevier Ltd. All rights reserved.
• Organocatalytic Enantioselective Pictet–Spengler Reactions for the Syntheses of 1-Substituted 1,2,3,4-Tetrahydroisoquinolines
  作者：Elma Mons、Martin J. Wanner、Steen Ingemann、Jan H. van Maarseveen、Henk Hiemstra

  DOI：10.1021/jo501099h

  日期：2014.8.15

  A series of 1-substituted 1,2,3,4-tetrahydroisoquinolines was prepared from N-(o-nitrophenylsulfenyl)phenylethylamines through BINOL-phosphoric acid [(R)-TRIP]-catalyzed asymmetric Pictet-Spengler reactions. The sulfenamide moiety is crucial for the rate and enantioselectivity of the iminium ion cyclization and the products are readily recrystallized to high enantiomeric purity. Using this methodology we synthesized the natural products (R)-crispine A, (R)-calycotomine and (R)-colchietine, the synthetic drug (R)-almorexant and the (S)-enantiomer of a biologically active (R)-AMPA-antagonist.