Efficient access to 3′-deoxy-3′-(4-substituted-1,2,3-triazol-1-yl)-thymidine derivatives via ligand-promoted CuAAC

Herein we describe an efficient and rapid access to 3′-deoxy-3′-(4-substituted-1,2,3-triazol-1-yl)-thymidine derivatives using 1,3-dipolar cycloaddition reaction catalyzed by copper(I). Innovative conditions allow us generate target compounds in a one-pot mixing 3′-azido-3′-deoxythymidine, alkyne, copper sulfate pentahydrate, sodium ascorbate tris(benzyltriazolylmethyl)amine water:tert-butanol solvent mixture. Rapid treatment of the subsequent flash purification chromatography afforded pure overall yield 71–100%. All eleven synthesized were identified on basis their spectral data analysis (1H, 13C, 2D NMR high-resolution mass spectra).