反应详情

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.

1. temperatureThe reaction was heated at 140° C. (MW) in a sealed tube for 2 h
2. washThe organic layer was washed with water (30 mL) and brine (50 mL)
3. dry with materialdried over Na2SO4
4. concentrationconcentrated to a residue which
5. customwas purified by chromatography
6. washeluted with PE/EA (10:1)