Herein we describe an efficient and rapid access to 3 0-deoxy-3 0-(4-substituted-1,2,3-triazol-1-yl)thymidine derivatives using 1,3-dipolar cycloaddition reaction catalyzed by copper(I). Innovative conditions allow us to generate target compounds in a one-pot reaction mixing 3 0-azido-3 0-deoxythymidine, alkyne, copper sulfate pentahydrate, sodium ascorbate and tris(benzyltriazolylmethyl)amine in a water:tert-butanol solvent mixture. Rapid treatment of the reaction and subsequent flash purification chromatography afforded pure compounds in an overall yield of 71e100%. All eleven synthesized compounds were identified on the basis of their spectral data analysis (1 H, 13 C, 2D NMR and highresolution mass spectra).