4-Chlorobenzaldehyde → 5-((4-chlorophenyl) (hydroxy)methyl)-1-methyl-6-(pyridin-3-yloxy)-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-methyl-6-(pyridin-3-yloxy)-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (400 mg, 0.97 mmol) in THF (8 mL) at −78° C. was added LDA (2M in THF, 1.94 mL, 3.88 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then a solution of 4-chlorobenzaldehyde (273.5 mg, 1.94 mmol) in THF (2 mL) was added dropwise. The reaction was stirred at −78° C. for 30 min. then diluted with EA (10 mL) and water (10 mL). The organic layer was dried over Na2SO4 and concentrated to a residue was purified by chromatography eluted with PE/EA (10:1 to 1:1) to give 5-((4-chlorophenyl) (hydroxy)methyl)-1-methyl-6-(pyridin-3-yloxy)-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (71 mg, 13.2% yield) as an oil. LCMS: [MH+-THP] 469 and TR=1.499 min.

Provenance & Evidence