N,N-Dimethylglycine → 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 Steps

To a suspension of 6-hydroxy-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 36, step 2, 600 mg, 1.8 mmol), CuI (45 mg, 0.23 mmol), Cs2CO3 (1.69 mg, 5.4 mmol) and 2-(dimethylamino)acetic acid (93 mg, 0.9 mmol) in dioxane (10 mL) was added 3-bromo-5-methylpyridine (0.45 mL, 3.6 mmol). The reaction was heated at 140° C. (MW) in a sealed tube for 2 h, cooled to RT and diluted with EA (50 mL) and water (50 mL). The organic layer was washed with water (30 mL) and brine (50 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (10:1) to give 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 (610 mg, 81% yield) as a yellow solid. LCMS MH+ 427 and TR=1.403 min.

Provenance & Evidence