This paper describes the application of the methylthiomethyl (MTM) protecting group for the N 1 position in differentially protected pyrrolo[2,3-d]pyrimidin-2,4-diones. By reaction of selected systems with SO 2 Cl 2 at low temperature resulted in selective formation of N 1 -chloromethyl derivatives. Subsequent heating in aqueous THF with silica gel afforded the deprotected compounds in good yield. Selectivity in the presence of N 3 methoxymethyl (MOM) and benzyloxymethyl (BOM), and N 7 p-nitrophenethyl protection was achieved.