Combine (R)-5-chloro-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (4.00 g, 11.6 mmol), 2-fluoro-4-iodoaniline (2.76 g, 11.6 mmol) and tetrahydrofuran (16.0 mL, 197 mmol). Cool to 0° C. to 5° C. in an ice bath, add 1.0 M lithium hexamethyldisilazide in tetrahydrofuran (23.3 mL, 23.3 mmol) while keeping the temperature below 10° C. Agitate in an ice bath for no less than 30 min and then warm to ambient temperature and stir overnight. Add water (20.0 mL) and methylene chloride (40.0 mL) and agitate, then separate the phases. Combine the organic phase and 40 mL of water, adjust the pH to 7 with 2 N HCl. Separate the organic phase extract with water (20 mL), dry over MgSO4, concentrate to 20 mL to give a solid. Add isopropyl acetate (40.0 mL, 342 mmol) to the suspension, stir at ambient temperature for no less than 2 hours, collect the solid by filtration, rinse with isopropyl acetate (20 mL), and dry overnight at 30° C. under vacuum to give the title compound.
