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

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To a mixture of 6-bromo-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 20, step 4, 500 mg, 1.26 mmol), N,N-dimethylglycine (65 mg, 0.631 mmol), CuI (30 mg, 0.158 mmol) and Cs2CO3 (821 mg, 2.52 mmol) in dioxane (10 mL) was added 3-(trifluoromethyl)phenol (306 mg, 1.89 mmol). The reaction was heated at 100° C. for 18 h followed by heating at 120° C. for 8 h, cooled to RT then diluted with EA (50 mL) and water (20 mL). The organic layer was washed with water (2×20 mL) and brine (20 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (6:1) to give 1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethyl)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (210 mg, 35% yield) as a white solid. LCMS: [M++Na] 502 and TR=1.626 min.

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