Microwave-Assisted Direct Amination: Rapid Access to Multi-Functionalized N6-Substituted Adenosines

Trent D. Ashton; Peter J. Scammells

doi:10.1071/CH07340

RESEARCH ARTICLE

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Microwave-Assisted Direct Amination: Rapid Access to Multi-Functionalized N⁶-Substituted Adenosines

Trent D. Ashton ^A and Peter J. Scammells ^A ^B

+ Author Affiliations

- Author Affiliations

^A Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Vic. 3052, Australia.

^B Corresponding author. Email: peter.scammells@vcp.monash.edu.au

Australian Journal of Chemistry 61(1) 49-58 https://doi.org/10.1071/CH07340
Submitted: 25 September 2007 Accepted: 9 November 2007 Published: 18 January 2008

Abstract

Analogues of adenosine have a range of interesting biological activities and potential therapeutic applications. A method for the efficient preparation of highly functionalized N⁶-substituted adenosines has been developed from the corresponding tert-butyldimethylsilyl-protected inosine. The key step in this procedure is a microwave-assisted amination reaction between an appropriately substituted inosine and an amine in the presence of PyBroP. High yields of desired N⁶-substituted adenosines were achieved with hindered amines and the reaction was also found to accommodate a range of substituents on the inosine precursor.

Acknowledgements

The authors thank Dr Simon Egan for the acquisition of mass spectrometric data.

References

^* δ_H 8.65 (s, 1H, H2/8), 8.52 (s, 1H, H8/2), 6.14 (d, J 5.1, 1H, H1′), 4.62 (app. t, J_app. 4.8, 1H, H2′), 4.32 (app. t, J_app. 3.9, 1H, H3′), 4.17 (app. d, J_app. 2.7, 1H, H4′), 4.02 (dd, J 11.4, 3.6, 1H, H5a′/b′), 3.82 (dd, J 11.4, 2.7, 1H, H5b′/a′), 3.48–3.42 (m, 12H, NCH₂CH₂), 2.00–1.96 (m, 12H, NCH₂CH₂), 0.96 (s, 9H, t-Bu), 0.94 (s, 9H, t-Bu), 0.78 (s, 9H, t-Bu), 0.16 (s, 3H, CH₃), 0.15 (s, 3H, CH₃), 0.11 (s, 6H, 2 × CH₃), –0.11 (s, 3H, CH₃), –0.27 (s, 3H, CH₃). δ_P 22.1 (s), –145.0 (sept, J 711.5). m/z (LRMS, 20 V) 850.5 (M – PF₆^–, 100%), 851.6 (65).

Microwave-Assisted Direct Amination: Rapid Access to Multi-Functionalized N6-Substituted Adenosines

Abstract

Acknowledgements

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Microwave-Assisted Direct Amination: Rapid Access to Multi-Functionalized N⁶-Substituted Adenosines