3-Methylbutanal → 5-(1-hydroxy-3-methylbutyl)-1-methyl-6-(5-methylpyridin-3-yloxy)-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 1-methyl-6-(5-methylpyridin-3-yloxy)-3-(3-(tetrahydro-2H-pyran-2-yloxy) propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 27, step 1, 100 mg, 0.23 mmol) in THF (5 mL) at −78° C. was added LDA (2M in THF, 0.48 mL, 0.940 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then 3-methylbutanal (40 mg, 0.470 mmol) in THF (1 mL) was added. The reaction was stirred at −78° C. for 45 min then diluted with DCM (10 mL) and water (10 mL). The organic layer was dried over Na2SO4 and concentrated to give 5-(1-hydroxy-3-methylbutyl)-1-methyl-6-(5-methylpyridin-3-yloxy)-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (120 mg, 90% yield) as a solid. LCMS: [M+-THP] 429 and TR=1.769 min. Used without further purification.

Provenance & Evidence