1,4-Dioxane → Ethyl 5-[1-[(2S)-2-methoxypropyl]-3-methyl-2-oxo-imidazo[4,5-c]quinolin-8-yl]pyridine-3-carboxylate

온도

85 °C

To a three-necked flask containing 8-bromo-1-[(2S)-2-methoxypropyl]-3-methyl-imidazo[4,5-c]quinolin-2-one (35 g, 100 mmol), ethyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-carboxylate (29.1 g, 105 mmol), sodium ethyl acetate (28.7 g, 350 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane (0.817 g, 1.0 mmol) add 1,4-dioxane (200 mL) and water (200 mL) under N2. Then heat the reaction mixture to 85° C. and continue stirring for 10 hours. Cool the reaction mixture to room temperature. Filter the mixture with Kieselguhr® Silica-Thiol to remove the catalyst. Add water (400 mL) drop wise and solid precipitates. Filter the mixture and wash the solid with water (400 mL). Stir the solid in ethyl acetate (70 mL) at room temperature for one hour; filter, wash with ethyl acetate (70 mL), and dry under vacuum below 65° C. to give the title compound (33.6 g, 80%). 1H NMR (CDCl3, 400 MHz) δ 9.25 (d, 1H, J=2 Hz), 9.15 (d, 1H, J=2.4 Hz), 8.75 (s, 1H), 8.73 (d, 1H, J=1.6 Hz), 8.65 (t, 1H), 8.24 (d, 1H, J=8.8 Hz), 7.89 (dt, 1H, J=8.8, 1.6 Hz), 4.47 (q, 2H), 4.38 (m, 2H), 3.90 (m, 1H), 3.64 (s, 3H), 3.26 (s, 3H), 1.45 (t, 3H), 1.37 (d, 3H, J=6 Hz).

1. temperatureCool the reaction mixture to room temperature
2. filtrationFilter the mixture with Kieselguhr® Silica-Thiol
3. customto remove the catalyst
4. customAdd water (400 mL) drop wise and solid precipitates
5. filtrationFilter the mixture
6. washwash the solid with water (400 mL)
7. stirringStir the solid in ethyl acetate (70 mL) at room temperature for one hour
8. filtrationfilter
9. washwash with ethyl acetate (70 mL)
10. customdry under vacuum below 65° C.

ORD 기록

ord-9d9bd455acf54bf694651401e09699d3

출처 데이터셋

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08658668B2