4-(Trifluoromethyl)benzaldehyde → 5-(hydroxy(4-(trifluoromethyl)phenyl)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethyl)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Participants

Reaction Conditions

Reaction Steps

To a solution of 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, 0.438 mmol) in THF (5 mL) at −78° C. was added LDA (1.8 M in THF, 1.2 mL, 2.16 mmol). The reaction was stirred at −78° C. for 30 min then 4-(trifluoromethyl)benzaldehyde (153 mg, 0.879 mmol) was added. The reaction was stirred for 1 h, quenched with aq. NaHCO3 (5 mL) then diluted with EA (10 mL) and water (10 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by Prep TLC eluted with PE/EA (4:1) to give 5-(hydroxy(4-(trifluoromethyl)phenyl)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethyl)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (200 mg, 69.9% yield) as a clear oil. LCMS: [MH+-THP] 570 and TR=1.933 min.

Provenance & Evidence