(Diethylamino)sulfur trifluoride → 2-chloro-11-fluoro-6-(fluoromethyl)-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole

Temperature

-78 °C

DAST (64 mg, 0.29 mmol) was added to a solution of (2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-6-yl)methanol (60 mg, 0.2 mmol) in CH2Cl2 (0.5 mL) at −78° C. under N2. The mixture was stirred at −78° C. for 1 hour. The mixture was then heated to reflux and stirred for another 3 hours. The mixture was then diluted with water (30 mL) and extracted with CH2Cl2 (15 mL*3). The organic layer was washed with brine (20 mL), dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using prep-TLC (petroleum ether:EtOAc=4:1) to provide 2-chloro-11-fluoro-6-(fluoromethyl)-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (30 mg, yield: 50.0%). 1H-NMR (CDCl3, 400 MHz) δ 7.29˜7.33 (m, 2H), 7.13˜7.20 (m, 2H), 7.03 (d, J=8.4 Hz, 1H), 6.78˜6.83 (m, 1H), 6.46˜6.51 (m, 1H), 4.35˜4.63 (m, 2H). MS (M+H)+: 307/309.

1. temperatureThe mixture was then heated
2. temperatureto reflux
3. stirringstirred for another 3 hours
4. extractionextracted with CH2Cl2 (15 mL*3)
5. washThe organic layer was washed with brine (20 mL)
6. dry with materialdried over Na2SO4
7. concentrationconcentrated in vacuo
8. customThe resulting residue was purified

ORD record

ord-7cd44b65cc8a462dbd0d4a060efa2c0c

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09265773B2