An Efficient and Safe Protocol for In-situ Generation of Azides for Click Chemistry: Late-Stage Application towards Synthesis of 1,2,3-Triazole Embedded Uridines

Nucleosides with heterocyclic side chains, such as 1,2,3triazoles are well known class of biologically active molecules. In this respect, alkyne nucleosides were found to be efficient synthons for synthesizing 1,2,3-triazoles via click chemistry. Although the selective propargylation of a nucleoside is challenging, it can be achieved by careful selection of suitable hydroxy protecting groups. On the other hand, the in-situ generation of azides from the corresponding amines is a safe protocol for click chemistry, but subsequent coherent reaction conditions play a crucial role in the success of 1,2,3-triazole synthesis in a nucleoside scaffold. Herein, we describe such a safe and efficient protocol for the synthesis of 1,2,3-triazole side chain containing nucleoside scaffold by selective propargylation of Uridine. This strategy afforded access to various, previously non-reported 1,2,3-triazole containing Uridine scaffolds and opens new avenue for such late-stage modifications in other nucleosides.