N,N-Dimethylglycine → 6-((5-fluoropyridin-3-yl)oxy)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy) propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

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To a mixture of 6-hydroxy-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 36, step 2, 300 mg, 0.90 mmol), CuI (22.5 mg, 0.19 mmol), Cs2CO3 (583.5 mg, 1.79 mmol) and 2-(dimethylamino)acetic acid (46.5 mg, 0.45 mmol) in dioxane (20 mL) was added 3-bromo-5-fluoropyridine (394 mg, 2.24 mmol). The reaction was heated at 140° C. for 5 h followed by heating at 100° C. for 18 h, cooled to RT then diluted with EA (25 mL) and water (10 mL). The organic layer was washed with water (20 mL) and brine (20 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (10:1 to 1:1) to give 6-((5-fluoropyridin-3-yl)oxy)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy) propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (150 mg, 38.9% yield) as a white solid. LCMS: [MH+-THP] 347 and TR=1.482 min.

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