Microwave-assisted direct amination: Rapid access to multi-functionalized N6-substituted adenosines

Analogues of adenosine have a range of interesting biological activities and potential therapeutic applications. A method for the efficient preparation of highly functionalized N-6-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.