General Synthesis of 3-Azabicyclo[3.1.1]heptanes and Evaluation of Their Properties as Saturated Isosteres

被引:50
作者
Dibchak, Dmitry [1 ]
Snisarenko, Mariya [1 ]
Mishuk, Artem [1 ]
Shablykin, Oleh [1 ,2 ]
Bortnichuk, Lina [3 ]
Klymenko-Ulianov, Oleksii [3 ]
Kheylik, Yurii [3 ]
Sadkova, Iryna V. V. [1 ]
Rzepa, Henry S. S. [4 ]
Mykhailiuk, Pavel K. K. [1 ]
机构
[1] Enamine Ltd, Chervonotkatska 60, UA-02094 Kiev, Ukraine
[2] Natl Acad Sci Ukraine, Inst Bioorgan Chem & Petrochem, Akad Kukharya 1, UA-02094 Kiev, Ukraine
[3] Bienta, Chervonotkatska 78, UA-02094 Kiev, Ukraine
[4] Imperial Coll London, Dept Chem, Mol Sci Res Hub, White City Campus,82 Wood Lane, London W12 0BZ, England
基金
欧洲研究理事会;
关键词
Bicyclo[1; 1; 1]Pentane; Bicyclo[3; 1]Heptane; Isosteres; Oxetanes; Spirocycles; CYCLOADDITIONS; OXETANES; AMINO;
D O I
10.1002/anie.202304246
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A general approach to 3-azabicyclo[3.1.1]heptanes by reduction of spirocyclic oxetanyl nitriles was developed. The mechanism, scope, and scalability of this transformation were studied. The core was incorporated into the structure of the antihistamine drug Rupatidine instead of the pyridine ring, which led to a dramatic improvement in physicochemical properties.
引用
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页数:8
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共 59 条
  • [1] A catalytic alkene insertion approach to bicyclo[2.1.1]hexane bioisosteres
    Agasti, Soumitra
    Beltran, Frederic
    Pye, Emma
    Kaltsoyannis, Nikolas
    Crisenza, Giacomo E. M.
    Procter, David J. J.
    [J]. NATURE CHEMISTRY, 2023, 15 (04) : 535 - +
  • [2] Enantioselective Desymmetrization of 3-Substituted Oxetanes: An Efficient Access to Chiral 3,4-Dihydro-2H-1,4-benzoxazines
    Bhosale, Viraj A.
    Nigrini, Martin
    Dracinsky, Martin
    Cisarova, Ivana
    Vesely, Jan
    [J]. ORGANIC LETTERS, 2021, 23 (24) : 9376 - 9381
  • [3] A Practical and Scalable Approach to Fluoro-Substituted Bicyclo[1.1.1]pentanes
    Bychek, Roman
    Mykhailiuk, Pavel K.
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2022, 61 (29)
  • [4] Synthesis and applications of highly functionalized 1-halo-3-substituted bicyclo[1.1.1]pentanes
    Caputo, Dimitri F. J.
    Arroniz, Carlos
    Durr, Alexander B.
    Mousseau, James J.
    Stepan, Antonia F.
    Mansfield, Steven J.
    Anderson, Edward A.
    [J]. CHEMICAL SCIENCE, 2018, 9 (23) : 5295 - 5300
  • [5] Synthesis of Spirocyclic Pyrrolidines: Advanced Building Blocks for Drug Discovery
    Chalyk, Bohdan A.
    Butko, Maryna V.
    Yanshyna, Oksana O.
    Gavrilenko, Konstantin S.
    Druzhenko, Tetiana V.
    Mykhailiuk, Pavel K.
    [J]. CHEMISTRY-A EUROPEAN JOURNAL, 2017, 23 (66) : 16782 - 16786
  • [6] 2-Oxabicyclo[2.1.1]hexanes as saturated bioisosteres of the ortho-substituted phenyl ring
    Denisenko, Aleksandr
    Garbuz, Pavel
    Voloshchuk, Nataliya M. M.
    Holota, Yuliia
    Al-Maali, Galeb
    Borysko, Petro
    Mykhailiuk, Pavel K. K.
    [J]. NATURE CHEMISTRY, 2023, 15 (08) : 1155 - +
  • [7] Saturated Bioisosteres ofortho-Substituted Benzenes
    Denisenko, Aleksandr
    Garbuz, Pavel
    Shishkina, Svetlana, V
    Voloshchuk, Nataliya M.
    Mykhailiuk, Pavel K.
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2020, 59 (46) : 20515 - 20521
  • [8] 3-Benzyl-3-azabicyclo[3.1.1]heptan-6-one: A Promising Building Block for Medicinal Chemistry
    Denisenko, Aleksandr V.
    Mityuk, Andrey P.
    Grygorenko, Oleksandr O.
    Volochnyuk, Dmytro M.
    Shishkin, Oleg V.
    Tolmachev, Andrey A.
    Mykhailiuk, Pavel K.
    [J]. ORGANIC LETTERS, 2010, 12 (19) : 4372 - 4375
  • [9] Mild Intramolecular Ring Opening of Oxetanes
    DeRatt, Lindsey G.
    Lawson, Edward C.
    Wang, Chao-Yuan
    Kuduk, Scott D.
    [J]. ORGANIC LETTERS, 2019, 21 (23) : 9642 - 9645
  • [10] Beyond Bioisosteres: Divergent Synthesis of Azabicyclohexanes and Cyclobutenyl Amines from Bicyclobutanes
    Dhake, Kushal
    Woelk, Kyla J.
    Becica, Joseph
    Un, Andy
    Jenny, Sarah E.
    Leitch, David C.
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2022, 61 (27)