4-Chlorobenzaldehyde → 5-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-6-((6-methylpyridin-3-yl)oxy)-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-((6-methylpyridin-3-yl)oxy)-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (450 mg, 1.06 mmol) in THF (8 mL) at −78° C. was added LDA (2M in THF, 2.11 mL, 4.24 mmol) dropwise. The reaction was stirred at −78° C. for 1 h. then a solution of 4-chlorobenzaldehyde (296.6 mg, 2.11 mmol) in THF (2 mL) was added dropwise. The reaction was stirred for 30 min at −78° C. 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 chromatography eluted with PE/EA (10:1 to 1:1) to give 5-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-6-((6-methylpyridin-3-yl)oxy)-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (40 mg, 6.7% yield) as an oil. LCMS: MH+ 567 and TR=1.400 min.

Provenance & Evidence