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

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (87 mg, 0.23 mmol) in THF (5 mL) cooled to −78° C. was added LDA (2.0 M in THF, 0.6 mL, 1.15 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then a solution of 4-chlorobenzaldehyde (64.8 mg, 0.46 mmol) in THF (1 mL) was added dropwise. The reaction was stirred at −78° C. for 1 h, quenched with aq. NH4Cl (5 mL), diluted with water (25 mL) then extracted with EA (3×25 mL). The combined organic layers were dried over Na2SO4 and concentrated to a residue which was purified by Prep TLC eluted with PE/EA (1:2) to give 5-((4-chlorophenyl)(hydroxy)methyl)-6-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy) propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (64 mg, 53.6% yield) as a white solid. LCMS: [M+-THP-OH] 416 and TR=3.210 min. Used without further purification.

Provenance & Evidence