反应详情

温度

30 °C

A solution of 2-chloro-6-methoxyquinolin-4-amine (4.50 g, 21.6 mmol) in HF-pyridine (45 mL) was cooled to −10-0° C. Then NaNO2 (1.80 g, 26.1 mmol) was added portionwise and the mixture was stirred at 0° C. for 1 hour and at 30° C. for 1 hour. Then the mixture was heated to 65° C. for 1.5 hours. The mixture was quenched with ice-water (100 mL); the aqueous layer was neutralized with 2 M NaOH to pH 7. The mixture was filtered off and the filtrate was extracted with EtOAc (50 mL×3), the organic layer was washed with brine (100 mL), dried over Na2SO4 and concentrated in vacuo. Purification by column chromatography on silica gel (PE/EtOAc=15/1) gave Intermediate 7 (3.60 g, yield: 40%). 1H NMR (CDCl3 400 MHz): δ 7.92 (dd, J=9.2, 1.6 Hz, 1H), 7.40 (dd, J=9.2, 2.8 Hz, 1H), 7.25 (s, 1H), 7.10 (d, J=9.2 Hz, 1H), 3.97 (s, 3H).

1. temperatureThen the mixture was heated to 65° C. for 1.5 hours
2. customThe mixture was quenched with ice-water (100 mL)
3. filtrationThe mixture was filtered off
4. extractionthe filtrate was extracted with EtOAc (50 mL×3)
5. washthe organic layer was washed with brine (100 mL)
6. dry with materialdried over Na2SO4
7. concentrationconcentrated in vacuo
8. customPurification by column chromatography on silica gel (PE/EtOAc=15/1)