Lithium diisopropylamide → 5-(hydroxy(6-(trifluoromethyl)-pyridin-3-yl)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

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To a solution of 1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethoxy) phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (156 mg, 0.32 mmol) in THF (6 mL) at −78° C. was added LDA (0.8 mL, 1.6 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then 6-(trifluoromethyl)nicotinaldehyde (112 mg, 0.64 mmol) in THF (3 mL) was added dropwise. The reaction was stirred at −78° C. for 45 min then diluted with DCM (10 mL) and water (10 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (4:6) to give 5-(hydroxy(6-(trifluoromethyl)-pyridin-3-yl)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (40 mg, 18.6% yield) as a solid. LCMS: [M+-THP-OH—H] 569 and TR=2.162 min.

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