4-Chlorobenzaldehyde → 5-((4-chlorophenyl)(hydroxy)methyl)-6-((5-chloropyridin-3-yl)oxy)-1-methyl-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 6-((5-chloropyridin-3-yl)oxy)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (470 mg, 1.06 mmol) in THF (10 mL) at −78° C. was added LDA (2M in THF, 2.12 mL, 4.24 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then 4-chlorobenzaldehyde (298.8 mg, 2.12 mmol) in THF (2 mL) was added. 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 which was purified by chromatography eluted with PE/EA (10:1 to 1:1) to give 5-((4-chlorophenyl)(hydroxy)methyl)-6-((5-chloropyridin-3-yl)oxy)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4 (1H,3H)-dione (120 mg, 19.4% yield) as an oil. LCMS: [MH+-THP] 503 and TR=1.508 min.

Provenance & Evidence