1-deutero-1,2,3,4-tetrahydroisoquinoline | 106181-29-7

• 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-deutero-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 1-Deuterio-tetrahydroisochinolin；1-deuterio-1,2,3,4-tetrahydroisoquinoline
• CAS: 106181-29-7
• 化学式: C₉H₁₁N
• 分子量: 134.185
• InChiKey: UWYZHKAOTLEWKK-WHRKIXHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-deutero-1,2,3,4-tetrahydroisoquinoline 在 哌啶 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 diethyl 2-[[2-(1-deuterio-3,4-dihydro-1H-isoquinolin-2-yl)phenyl]methylidene]propanedioate
  参考文献：
  名称：

  不对称二元酸催化（ABC）催化对映选择性叔氨基环化：立体定向的1,5-氢转移

  摘要：

  通过ABC进行的选择性H转移：开发了一种新型的不对称二元酸催化剂，可在叔氨基环化反应中特异性和立体选择性地促进1,5-H转移，具有出色的活性，高对映选择性和广泛的底物范围。事实证明，H原子（红色）通过立体特异性表面途径转移（参见方案）。

  DOI：

  10.1002/chem.201201532
• 作为产物：
  描述：

  3,4-二氢异喹啉 在 硼氘化钠 、 乙醇 作用下， 反应 1.0h， 以5.26 g的产率得到1-deutero-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  不对称二元酸催化（ABC）催化对映选择性叔氨基环化：立体定向的1,5-氢转移

  摘要：

  通过ABC进行的选择性H转移：开发了一种新型的不对称二元酸催化剂，可在叔氨基环化反应中特异性和立体选择性地促进1,5-H转移，具有出色的活性，高对映选择性和广泛的底物范围。事实证明，H原子（红色）通过立体特异性表面途径转移（参见方案）。

  DOI：

  10.1002/chem.201201532

文献信息

• Carbon dioxide: A reagent for the protection of nucleophilic centres and the simultaneous activation of electrophilic attack
  作者：Alan R. Katritzky、Kunihiko Akutagawa

  DOI：10.1016/0040-4020(86)80024-2

  日期：1986.1

  Tetrahydroisoquinoline was converted into several 1-substituted derivatives by using carbon dioxide both for N-protection and to give an intermediate carbanion stabilizing group. t-Butyllithium was used as a lithating agent at the alphacarbon atom of the secondary amino group. The resulting 1-substituted 1,2,3,4-tetrahydroisoquinoline-2-carboxylic acids underwent smooth acid-catalysed decarboxylation

  通过使用二氧化碳进行N-保护和提供中间碳负离子稳定基团，将四氢异喹啉转化为几种1-取代的衍生物。在仲氨基的α碳原子处，叔丁基锂被用作锂化剂。在温和的条件下，将所得的1-取代的1,2,3,4-四氢异喹啉-2-羧酸进行平滑的酸催化脱羧。
• Evaluation of Phenyldiazenyl as a Protective/Activating Group in Lithiation–Substitution Reactions of Tetrahydroisoquinolines
  作者：Kamal Nain Singh、Babaldeep Kaur、Manjot Kaur、Pushpinder Singh、Esha Sharma、Aanchal Batra、Amarjit Kaur

  DOI：10.1055/s-0042-1751537

  日期：——

  Phenyldiazenyl moiety has been utilized both as a protective and activating group to synthesize C-1-substituted tetrahydroisoquinolines via lithiation–substitution strategy. This reaction sequence involves generation of α-amino carbanions, derived from N-phenyldiazenyl tetrahydroisoquinolines, followed by coupling with various electrophiles, e.g., aldehyde, ketones, alkyl halide, oxiranes, isocyanates

  苯基二氮烯基部分已被用作保护基团和活化基团，通过锂化-取代策略合成 C-1-取代的四氢异喹啉。该反应顺序涉及生成源自 N-苯基二氮烯基四氢异喹啉的 α-氨基碳负离子，然后与各种亲电子试剂（例如醛、酮、卤代烷、环氧乙烷、异氰酸酯）以及原位生成的芳烃偶联。在酸性条件下进行保护基团的脱保护，以中等至良好的产率提供所需的α-取代产物。因此，三氮烯​​作为保护/导向基团及其与强碱的相容性为通过锂化取代反应合成各种α-取代仲胺提供了良好的合成实用性。
• Tetrahydroisoquinolines as selective NADPH oxidase 2 inhibitors
  申请人：University of Pittsburgh—Of the Commonwealth System of Higher Education

  公开号：US10906876B2

  公开（公告）日：2021-02-02

  Embodiments of bridged tetrahydroisoquinolines and methods for their use in selectively inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 are disclosed. The disclosed compounds have a structure according to general formula I or a pharmaceutically acceptable salt thereof: wherein “” represents a single or double bond, R1 is hydrogen, halogen, lower aliphatic, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Ra is hydrogen, —CH2R2, R3, or —SO2R4; R2 is lower aliphatic, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R3 is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R4 is lower aliphatic, or substituted or unsubstituted aryl; and R5 is hydrogen, halogen, or lower aliphatic.

  本发明公开了桥式四氢异喹啉的实施方案及其用于选择性抑制烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶2的方法。所公开的化合物具有通式 I 的结构或其药学上可接受的盐： 其中""代表单键或双键，R1是氢、卤素、低脂族、取代或未取代的芳基或取代或未取代的杂芳基；Ra是氢、-CH2R2、R3或-SO2R4；R2 是低级脂肪族、取代或未取代的芳基、取代或未取代的杂芳基； R3 是取代或未取代的芳基、取代或未取代的杂芳基； R4 是低级脂肪族、取代或未取代的芳基；以及 R5 是氢、卤素或低级脂肪族。
• Bioinspired Aerobic Oxidation of Secondary Amines and Nitrogen Heterocycles with a Bifunctional Quinone Catalyst
  作者：Alison E. Wendlandt、Shannon S. Stahl

  DOI：10.1021/ja411692v

  日期：2014.1.8

  Copper amine oxidases are a family of enzymes with quinone cofactors that oxidize primary amines to aldehydes. The native mechanism proceeds via an iminoquinone intermediate that promotes high selectivity for reactions with primary amines, thereby constraining the scope of potential biomimetic synthetic applications. Here we report a novel bioinspired quinone catalyst system consisting of 1,10-phenanthroline-5,6-dione/ZnI2 that bypasses these constraints via an abiological pathway involving a hemiaminal intermediate. Efficient aerobic dehydrogenation of non-native secondary amine substrates, including pharmaceutically relevant nitrogen heterocycles, is demonstrated. The ZnI2 cocatalyst activates the quinone toward amine oxidation and provides a source of iodide, which plays an important redox-mediator role to promote aerobic catalytic turnover. These findings provide a valuable foundation for broader development of aerobic oxidation reactions employing quinone-based catalysts.
• Metal-Free α-Amination of Secondary Amines: Computational and Experimental Evidence for Azaquinone Methide and Azomethine Ylide Intermediates
  作者：Arne Dieckmann、Matthew T. Richers、Alena Yu. Platonova、Chen Zhang、Daniel Seidel、K. N. Houk

  DOI：10.1021/jo400483h

  日期：2013.4.19

  We have performed a combined computational and experimental study to elucidate the mechanism of a metal-free alpha-amination of secondary amines. Calculations predicted azaquinone methides and azomethine ylides as the reactive intermediates and showed that iminium ions are unlikely to participate in these transformations. These results were confirmed by experimental deuterium-labeling studies and the successful trapping of the postulated azomethine ylide and azaquinone methide intermediates. In addition, computed barrier heights for the rate-limiting step correlate qualitatively with experimental findings.