1-(2'-bromobenzyl)-N-tert-butyloxycarbonyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline | 839673-82-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1-(2'-bromobenzyl)-N-tert-butyloxycarbonyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
• 英文别名: tert-butyl 1-[(2-bromophenyl)methyl]-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxylate
• CAS: 839673-82-4
• 化学式: C₂₃H₂₈BrNO₄
• 分子量: 462.384
• InChiKey: FHNWOIZMSMVVBF-UHFFFAOYSA-N

物化性质

• 沸点：
  535.0±50.0 °C(Predicted)
• 密度：
  1.295±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2'-bromobenzyl)-N-tert-butyloxycarbonyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 在 palladium diacetate 、 三溴化硼 、 potassium carbonate 、 cesium fluoride 、 potassium hydroxide 、 nuciferine 、 2-二苯基磷-2'-(N,N-二甲氨基)联苯 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 20.0h， 生成
  参考文献：
  名称：

  3,4-Dihydroxy- and 3,4-methylenedioxy- phenanthrene-type alkaloids with high selectivity for D2 dopamine receptor

  摘要：

  Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new drugs acting at the dopamine receptors (DR) as potential new targets for the treatment of schizophrenia or Parkinson's disease. Previous studies have revealed that isoquinoline compounds such as tetrahydroisoquinolines (THIQs) can behave as selective D-2 dopaminergic alkaloids. In the present study we have synthesized five aporphine compounds and five phenanthrene alkaloids and evaluated their potential dopaminergic activity. Binding studies on rat striatal membranes were used to evaluate their affinity and selectivity towards D-1 and D-2 DR. Phenanthrene type alkaloids, in particular the 3,4-dihydroxy- and 3,4-methylenedioxy derivatives, displayed high selectivity towards D-2 DR. Therefore, they are potential candidates to be used in the treatment of schizophrenia (antagonists) or Parkinson's disease (agonists) due to their scarce D-1 DR-associated side effects. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.078
• 作为产物：
  描述：

  邻溴苯乙酸 在 4-二甲氨基吡啶 光气 、 sodium tetrahydroborate 、 三乙胺 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 1-(2'-bromobenzyl)-N-tert-butyloxycarbonyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  通过直接芳基化合成阿朴啡生物碱并使其多样化

  摘要：

  钯催化的芳基氯化物、溴化物和碘化物的直接芳基化已被应用于通过与苯并二恶唑、吡啶 N-氧化物和吡嗪 N-氧化物反应制备新的阿朴啡类似物，包括 C2 取代的阿朴啡。直接芳基化在这些多样化反应中的成功应用突出了其不仅在收敛合成中而且在发散合成中的效用。我们还描述了 (R)-nornuciferine 和 (R)-nuciferine 的对映选择性合成，采用催化不对称转移氢化以高产率和优异的对映体过量。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

  DOI：

  10.1002/ejoc.200600674

文献信息

• Mild and efficient palladium-catalyzed intramolecular direct arylation reactions
  作者：Marc Lafrance、David Lapointe、Keith Fagnou

  DOI：10.1016/j.tet.2008.01.057

  日期：2008.6

  been evaluated in the context of intramolecular direct arylation reactions. Under the optimal conditions, arylation of simple arenes can be performed under very mild conditions, with heating to 50 °C. The role of the pivalic acid additive is rationalized by invoking a concerted palladation–deprotonation pathway where the pivalate is behaving as either an intramolecular base from the palladium metal or

  配体，化学计量的碱和添加剂的影响已在分子内直接芳基化反应的背景下进行了评估。在最佳条件下，简单的芳烃芳构化可以在非常温和的条件下进行，加热到50°C。新戊酸添加剂的作用可通过调用协调的palladation-去质子化途径来合理化，在该途径中，新戊酸酯以钯金属的分子内碱或分子间去质子的方式表现为与Echavarren和Maseras先前描述的方式类似的方式。
• Microwave-assisted direct biaryl coupling: first application to the synthesis of aporphines
  作者：Sandeep Chaudhary、Stevan Pecic、Onica LeGendre、Wayne W. Harding

  DOI：10.1016/j.tetlet.2009.03.029

  日期：2009.5

  microwaves in a direct biaryl coupling reaction for the synthesis of analogs of the aporphine alkaloid nantenine. Our study shows that the aporphine core may be rapidly accessed from benzyl-tetrahydroisoquinoline substrates with this method. This is the first report of a microwave-assisted direct biaryl coupling reaction in the synthesis of aporphine molecules.

  我们研究了微波在直接联芳基偶联反应中用于合成阿朴啡生物碱 nantenine 类似物的用途。我们的研究表明，使用这种方法可以从苄基四氢异喹啉底物快速获得阿朴啡核心。这是阿朴啡分子合成中微波辅助直接联芳基偶联反应的首次报道。
• 1-(2′-Bromobenzyl)-6,7-dihydroxy-<i>N</i>-methyl-tetrahydroisoquinoline and 1,2-Demethyl-nuciferine as Agonists in Human D₂ Dopamine Receptors
  作者：Andrea G. Silva、Laura Vila、Patrice Marques、Laura Moreno、Mabel Loza、María-Jesús Sanz、Diego Cortes、Marián Castro、Nuria Cabedo

  DOI：10.1021/acs.jnatprod.9b00921

  日期：2020.1.24

  Certain D-2-like dopamine receptor (DR) agonists are useful therapeutically as antiparkinsonian drugs, whereas D-2-like DR antagonists or partial agonists are proven effective as antipsychotics. Two isoquinoline derivatives, 1-(2'-bromobenzy1)-6,7-dihydroxy-N-methyl-tetrahydroisoquinoline (Br-BTHIQ, 1) and 1,2-demethyl-nuciferine (aporphine, 2), were herein synthesized, and their dopaminergic affinity in cloned human D2R, D3R, and D4R subtypes and their behavior as agonists/antagonists were evaluated. They showed affinity values (K-i) for hD(2), hD(3), and hD(4) DR within the nanomolar range. The trends in affinity were hD(4)R >> hD(3)R > hD(2)R for Br-BTHIQ (1) and hD(2)R > hD(4)R > hD(3)R for 1,2-demethyl-nuciferine (2). The functional assays of cyclic adenosine monophosphate signaling at human D2R showed a partial agonist effect for Br-BTHIQ (1) and full agonist behavior for aporphine (2), with half maximal effective concentration values of 2.95 and 10.2 mu M, respectively. Therefore, both isoquinolines 1 and 2 have emerged as lead molecules for the synthesis of new therapeutic drugs that ultimately may be useful to prevent schizophrenia and Parkinson's disease, respectively.
• Total Synthesis of (±)-Armepavines and (±)-Nuciferines From (2-Nitroethenyl)benzene Derivatives
  作者：Chia-Fu Chang、Chu-Yun Huang、Yu-Chao Huang、Kuan-Yu Lin、Yean-Jang Lee、Chau-Jong Wang

  DOI：10.1080/00397910903435411

  日期：2010.11.3

  A concise route to armepavine 1 and nuciferine 2 and 3, which can be isolated from the leaves of Nelumbo nucifera (Nymphaceae), has been achieved in which the longest linear sequence is only six steps from commercially available benzaldehyde in 28%, 21%, and 20% overall yield, respectively. The key transformations in the synthesis are the radical cyclization of aryl bromide with Bu3SnH and the Pictet-Spengler reaction of N-substituted amine with aldehyde.