3-Methylbutanal → 5-(1-hydroxy-3-methylbutyl)-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, 2.0 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then 3-methylbutanal (68.8 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 (5 mL) diluted with water (13 mL) then extracted with EA (30 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-(1-hydroxy-3-methylbutyl)-6-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (60 mg, 32.4% yield) as a white solid. LCMS: [M+-THP-OH] 362 and TR=2.616 min.

Provenance & Evidence