N,N-Dimethylglycine → 6-((5-fluoropyridin-3-yl)oxy)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy) propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

온도

140 °C

To a mixture 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, 300 mg, 0.90 mmol), CuI (22.5 mg, 0.19 mmol), Cs2CO3 (583.5 mg, 1.79 mmol) and 2-(dimethylamino)acetic acid (46.5 mg, 0.45 mmol) in dioxane (20 mL) was added 3-bromo-5-fluoropyridine (394 mg, 2.24 mmol). The reaction was heated at 140° C. for 5 h followed by heating at 100° C. for 18 h, cooled to RT then diluted with EA (25 mL) and water (10 mL). The organic layer was washed with water (20 mL) and brine (20 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (10:1 to 1:1) to give 6-((5-fluoropyridin-3-yl)oxy)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy) propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (150 mg, 38.9% yield) as a white solid. LCMS: [MH+-THP] 347 and TR=1.482 min.

1. temperatureby heating at 100° C. for 18 h
2. temperaturecooled to RT
3. washThe organic layer was washed with water (20 mL) and brine (20 mL)
4. dry with materialdried over Na2SO4
5. concentrationconcentrated to a residue which
6. customwas purified by chromatography
7. washeluted with PE/EA (10:1 to 1:1)

ORD 기록

ord-5c5ba2ab3e134f108c041acd25c0f0b3

출처 데이터셋

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09440972B2