(S)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline | 136905-00-5

• 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)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline；(1S)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline
• CAS: 136905-00-5
• 化学式: C₁₇H₁₉NO₂
• mdl: MFCD00218177
• 分子量: 269.343
• InChiKey: GZGZWZVAJDFXJK-KRWDZBQOSA-N

物化性质

• 熔点：
  133.5-135 °C(Solv: ethanol (64-17-5))
• 沸点：
  400.9±45.0 °C(Predicted)
• 密度：
  1.101±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline 在 乙基氯化镁 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 4.5h， 生成 N-[2-[5-[6-[(1S)-6,7-dimethoxy-1-phenyl-3,4-dihydro-1H-isoquinolin-2-yl]hexyl]triazol-1-yl]ethyl]-1,2,3,4-tetrahydroacridin-9-amine
  参考文献：
  名称：

  In Situ Selection of Lead Compounds by Click Chemistry:  Target-Guided Optimization of Acetylcholinesterase Inhibitors

  摘要：

  The target-guided, in situ click chemistry approach to lead discovery has been successfully employed for discovering acetylcholinesterase (AChE) inhibitors by incubating a selected enzyme/tacrine azide combination with a variety of acetylene reagents that were not previously known to interact with the enzyme's peripheral binding site. The triazole products, formed by the enzyme, were identified by HPLC-mass spectrometry analysis of the crude reaction mixtures. The target-guided lead discovery search was also successful when performed with reagent mixtures containing up to 10 components. From 23 acetylene reagents, the enzyme selected two phenyltetrahydroisoquinoline (1310) building blocks that combined with the tacrine azide within the active center gorge to form multivalent inhibitors that simultaneously associate with the active and peripheral binding sites. These new inhibitors are up to 3 times as potent as our previous phenylphenanthridinium-derived compounds, and with dissociation constants as low as 33 femtomolar, they are the most potent noncovalent AChE inhibitors known. In addition, the new compounds lack a permanent positive charge and aniline groups and possess fewer fused aromatic rings. Remarkably, despite the high binding affinity, the enzyme displayed a surprisingly low preference for one IQ enantionner over the other.

  DOI：

  10.1021/ja043031t
• 作为产物：
  描述：

  3,4-二甲氧基苯乙胺 在 2-氯吡啶 、 bis(1,5-cyclooctadiene)diiridium(I) dichloride 、 三氟甲磺酸酐 、 C₄₂H₄₆FeP₂ 、 氢溴酸 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， -78.0~30.0 ℃ 、5.07 MPa 条件下， 反应 24.0h， 生成 (S)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Josiphos型Binaphane配体用于铱催化的1-芳基取代的二氢异喹啉的对映选择性加氢。

  摘要：

  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。

  DOI：

  10.1021/acs.orglett.9b03251

文献信息

• Kinetic Resolution of Nitrogen Heterocycles with a Reusable Polymer-Supported Reagent
  作者：Imants Kreituss、Yuta Murakami、Michael Binanzer、Jeffrey W. Bode

  DOI：10.1002/anie.201204991

  日期：2012.10.15

  Shake it up baby! Simply shaking a polymer‐supported reagent and the racemic amine at room temperature kinetically resolves a broad range of N‐heterocycles with good selectivity. The polymer‐supported reagents are robust, easy to regenerate, and can be reused dozens of times. Cleavable acyl groups can be used to give access to both amine enantiomers in a single resolution.

  摇摇宝贝！只需在室温下摇晃聚合物支撑的试剂和外消旋胺，就可以动力学分离宽范围的N-杂环，并具有良好的选择性。聚合物支持的试剂坚固耐用，易于再生，可以重复使用数十次。可裂解的酰基可用于以单一分辨率获得两种胺对映体。
• Asymmetric Hydrogenation of Isoquinolines and Pyridines Using Hydrogen Halide Generated in Situ as Activator
  作者：Mu-Wang Chen、Yue Ji、Jie Wang、Qing-An Chen、Lei Shi、Yong-Gui Zhou

  DOI：10.1021/acs.orglett.7b02502

  日期：2017.9.15

  traceless activation reagent, a general iridium-catalyzed asymmetric hydrogenation of isoquinolines and pyridines is developed with up to 99% ee. This method avoids tedious steps of installation and removal of the activating groups. The mechanism studies indicated that hydrogen halide generated in situ acted as an activator of isoquinolines and pyridines.

  通过使用卤化物三氯异氰尿酸作为无痕活化剂，可以开发出具有高达99％ee的一般铱催化的异喹啉和吡啶的不对称氢化反应。该方法避免了安装和拆卸活化基团的繁琐步骤。机理研究表明，原位产生的卤化氢起异喹啉和吡啶的活化剂作用。
• Stereoelectronic Basis for the Kinetic Resolution of N-Heterocycles with Chiral Acylating Reagents
  作者：Sheng-Ying Hsieh、Benedikt Wanner、Philip Wheeler、André M. Beauchemin、Tomislav Rovis、Jeffrey W. Bode

  DOI：10.1002/chem.201402818

  日期：2014.6.10

  The kinetic resolution of N‐heterocycles with chiral acylating agents reveals a previously unrecognized stereoelectronic effect in amine acylation. Combined with a new achiral hydroxamate, this effect makes possible the resolution of various N‐heterocycles by using easily prepared reagents. A transition‐state model to rationalize the stereochemical outcome of this kinetic resolution is also proposed

  N-杂环与手性酰化剂的动力学拆分揭示了胺酰化中以前未被认识的立体电子效应。与新的非手性异羟肟酸酯相结合，这种效应使得通过使用易于制备的试剂来拆分各种N-杂环成为可能。还提出了一种过渡态模型来合理化这种动力学解析的立体化学结果。
• A Highly Efficient and Enantioselective Access to Tetrahydroisoquinoline Alkaloids: Asymmetric Hydrogenation with an Iridium Catalyst
  作者：Mingxin Chang、Wei Li、Xumu Zhang

  DOI：10.1002/anie.201104476

  日期：2011.11.4

  Efficient and enantioselective: Using the iodine‐bridged dimeric iridium complex [Ir(H)[(S,S)‐(f)‐binaphane]}2(μ‐I)3]+I− (1) a wide range of tetrahydroisoquinoline alkaloids, including the substructure of the pharmaceutical drug solifenacin, were obtained with excellent enantioselectivities and high turnover numbers (see scheme).

  高效和对映选择性：使用碘桥接的二聚体铱络合物[的Ir（H）[（小号，小号） - （F）-binaphane]} 2（μ-I）3 ] +我- （1）广泛的获得了四氢异喹啉碱生物碱，包括药物索非那新的亚结构，具有出色的对映选择性和高周转率（参见方案）。
• Enantioselective Synthesis of 1-Aryl-Substituted Tetrahydroisoquinolines Through Ru-Catalyzed Asymmetric Transfer Hydrogenation
  作者：Marc Perez、Zi Wu、Michelangelo Scalone、Tahar Ayad、Virginie Ratovelomanana-Vidal

  DOI：10.1002/ejoc.201500951

  日期：2015.9

  A convenient and general asymmetric transfer hydrogenation of a wide array of 1-aryl-3,4-dihydroisoquinoline derivatives using a [RuIICl(η6-benzene)TsDPEN] complex in combination with a 5:2 HCOOH–Et3N azeotropic mixture as a hydrogen source was developed. Under mild reaction conditions, the described catalytic transformation secured a practical synthetic access to the corresponding valuable chiral

  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。