3-Methylbutanal → 6-bromo-5-(1-hydroxy-3-methylbutyl)-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-bromo-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 20, step 4, 300 mg, 0.753 mmol) in THF (10 mL) at −78° C. was added LDA (1.8M in THF, 2.1 mL, 3.765 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then 3-methylbutanal (129.8 mg, 1.506 mmol) in THF (2 mL) was added. The reaction was stirred at −78° C. for 30 min then diluted with DCM (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 give 6-bromo-5-(1-hydroxy-3-methylbutyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (65 mg, 17.8% yield) as a solid. LCMS: [M+-THP-OH] 382 and TR=2.155 min.

Provenance & Evidence