Microwave-Assisted Direct Amination: Rapid Access to Multi-Functionalized N6-Substituted Adenosines
Trent D. Ashton A and Peter J. Scammells A BA 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.
[1]
H. O. Kim,
X.-D. Ji,
S. M. Siddiqi,
M. E. Olah,
G. L. Stiles,
K. A. Jacobson,
J. Med. Chem. 1994, 37, 3614.
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* δH 8.65 (s, 1H, H2/8), 8.52 (s, 1H, H8/2), 6.14 (d, J 5.1, 1H, H1′), 4.62 (app. t, Japp. 4.8, 1H, H2′), 4.32 (app. t, Japp. 3.9, 1H, H3′), 4.17 (app. d, Japp. 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). δP 22.1 (s), –145.0 (sept, J 711.5). m/z (LRMS, 20 V) 850.5 (M – PF6–, 100%), 851.6 (65).