The esterification of 2,2-dimethyl-thiopropionic acid (I) with 2-iodoethanol (II) and DBU in toluene gives the corresponding thioester (III), which is condensed with diisopropylamidophosphoryl dichloride (IV) by means of TEA in THF to afford the phosphoramidite (V). Finally, this compound is condensed with AZT (VI) by means of 1H-tetrazole and MCPBA or 1H-tetrazole and tert-butyl peroxide, both cases in THF.
The phosphorylation of AZT (VI) with POCl3 trimethyl phosphate gives the 5'-O-phosphate (VII), which is then condensed with the previously described thioester (III) by means of Tps-Cl in pyridine.