Lithium diisopropylamide → 6-bromo-5-((5-chloropyridin-2-yl)(hydroxy)methyl)-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-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, 398 mg, 0.10 mmol) in THF (10 mL) at −78° C. was added LDA (2M in THF, 2.50 mL, 5.00 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then 5-chloropicolinaldehyde (211 mg, 1.50 mmol) in THF (2 mL) was added. The reaction was stirred at −78° C. for 40 min then diluted with EA (20 mL) and water (10 mL). The organic layer was washed with brine (30 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (8:1) to give 6-bromo-5-((5-chloropyridin-2-yl)(hydroxy)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (75 mg, 13.9% yield) as a solid. LCMS: MH+ 541 and TR=1.773 min.

Provenance & Evidence