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

被引：65

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

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2023年 / 62卷 / 39期

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

页数：8

共 59 条

[1] A catalytic alkene insertion approach to bicyclo[2.1.1]hexane bioisosteres [J].

Agasti, Soumitra ;

Beltran, Frederic ;

Pye, Emma ;

Kaltsoyannis, Nikolas ;

Crisenza, Giacomo E. M. ;

Procter, David 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 [J].

Bhosale, Viraj A. ;

Nigrini, Martin ;

Dracinsky, Martin ;

Cisarova, Ivana ;

Vesely, Jan .

ORGANIC LETTERS, 2021, 23 (24) :9376-9381

[3] A Practical and Scalable Approach to Fluoro-Substituted Bicyclo[1.1.1]pentanes [J].

Bychek, Roman ;

Mykhailiuk, Pavel K. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2022, 61 (29)

[4] Synthesis and applications of highly functionalized 1-halo-3-substituted bicyclo[1.1.1]pentanes [J].

Caputo, Dimitri F. J. ;

Arroniz, Carlos ;

Durr, Alexander B. ;

Mousseau, James J. ;

Stepan, Antonia F. ;

Mansfield, Steven J. ;

Anderson, Edward A. .

CHEMICAL SCIENCE, 2018, 9 (23) :5295-5300

[5] Synthesis of Spirocyclic Pyrrolidines: Advanced Building Blocks for Drug Discovery [J].

Chalyk, Bohdan A. ;

Butko, Maryna V. ;

Yanshyna, Oksana O. ;

Gavrilenko, Konstantin S. ;

Druzhenko, Tetiana V. ;

Mykhailiuk, Pavel K. .

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 [J].

Denisenko, Aleksandr ;

Garbuz, Pavel ;

Voloshchuk, Nataliya M. M. ;

Holota, Yuliia ;

Al-Maali, Galeb ;

Borysko, Petro ;

Mykhailiuk, Pavel K. K. .

NATURE CHEMISTRY, 2023, 15 (08) :1155-+

[7] Saturated Bioisosteres ofortho-Substituted Benzenes [J].

Denisenko, Aleksandr ;

Garbuz, Pavel ;

Shishkina, Svetlana, V ;

Voloshchuk, Nataliya M. ;

Mykhailiuk, Pavel K. .

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 [J].

Denisenko, Aleksandr V. ;

Mityuk, Andrey P. ;

Grygorenko, Oleksandr O. ;

Volochnyuk, Dmytro M. ;

Shishkin, Oleg V. ;

Tolmachev, Andrey A. ;

Mykhailiuk, Pavel K. .

ORGANIC LETTERS, 2010, 12 (19) :4372-4375

[9] Mild Intramolecular Ring Opening of Oxetanes [J].

DeRatt, Lindsey G. ;

Lawson, Edward C. ;

Wang, Chao-Yuan ;

Kuduk, Scott D. .

ORGANIC LETTERS, 2019, 21 (23) :9642-9645

[10] Beyond Bioisosteres: Divergent Synthesis of Azabicyclohexanes and Cyclobutenyl Amines from Bicyclobutanes [J].

Dhake, Kushal ;

Woelk, Kyla J. ;

Becica, Joseph ;

Un, Andy ;

Jenny, Sarah E. ;

Leitch, David C. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2022, 61 (27)

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