Benzaldehyde → 5-(hydroxy(phenyl)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 (See Compound 36, step 3, 150 mg, 0.4 mmol) in THF (6 mL) at −78° C. was added LDA (2M in THF, 1.0 mL, 2 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then benzaldehyde (84.8 mg, 0.8 mmol) in THF (1.5 mL) was added. The reaction was stirred at −78° C. for 1 h quenched with aq. NH4Cl (8 mL) then diluted with EA (30 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 (2:1) to give 5-(hydroxy(phenyl)methyl)-6-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (100 mg, 51.8% yield) as a solid. LCMS: [M+-THP-OH] 382 and TR=1.855 min.

Provenance & Evidence