2-Chloro-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (384 mg, 1.508 mmol), 2,2-difluoropropyl 4-nitrobenzenesulfonate (767 mg, 2.73 mmol), cesium carbonate (1240 mg, 3.81 mmol) were combined in DMA (2 mL) at ambient temperature for about 1 hour and then heated in an oil bath at 60° C. After about 22 hours, the reaction mixture was allowed to cool to ambient temperature, diluted reaction mixture with 25 mL EtOAc, transferred to a separatory funnel, and the reaction vessel rinsed twice with 10 mL 1:1 EtOAc/water. An additional 10 mL of water was then added, the layers were mixed and then separated. The organic layer was extracted with water (10 mL) and the combined aqueous layers were extracted with 10 mL of EtOAc, which was then extracted with 5 mL brine. The combined organic layers were dried over sodium sulfate, filtered, and concentrated on a rotovap to give a residue. The residue was combined with isopropanol (5 mL) and heated in an oil bath at 50° C. oil bath. An addition 1.5 mL was added and the solution was allowed to cool to ambient temperature with stirring to give a solid. Collected the solid by filtration, rinse the filter cake with 1 mL isopropanol and air dry for 2 hours, then dry under vacuum to give the title compound.
