2-Fluoroaniline → HCID 62155572, compound

Temperature

130 °C

A mixture of 2-Amino-5-bromo-nicotinic acid (1 g, 4.61 mmol) and SOCl2 (5 mL) in toluene (15 mL) was stirred at 130° C. for 2 h. After concentrated, the residue was dissolved in tetrahydrofuran (20 mL), and then 2-fluoro-phenylamine (1.09 g, 9.81 mmol) was added dropwise at 0° C. The reaction mixture was heated to 90° C. for 4 h. After being cooled to room temperature and quenched with saturated aqueous K2 CO3 (10 mL), the mixture was extracted with ethyl acetate (50 mL*3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified with silica gel column chromatograph (PE:EtOAc=2:1) to give 2-amino-5-bromo-N-(2-fluorophenyl)nicotinamide (1.0 g, 70% yield) as yellow solid. 1H-NMR (CDCl3, 400 MHz) δ 8.25˜8.28 (m, 2H), 7.86 (d, J=2.4 Hz, 2H), 7.13˜7.22 (m, 3H), 6.36 (s, 2H). MS (M+H)+: 311/313.

1. concentrationAfter concentrated
2. dissolutionthe residue was dissolved in tetrahydrofuran (20 mL)
3. temperatureThe reaction mixture was heated to 90° C. for 4 h
4. temperatureAfter being cooled to room temperature
5. customquenched with saturated aqueous K2 CO3 (10 mL)
6. extractionthe mixture was extracted with ethyl acetate (50 mL*3)
7. washThe combined organic layers were washed with brine
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customThe residue was purified with silica gel column chromatograph (PE:EtOAc=2:1)

ORD record

ord-a0746dc9f0724225bb274289a031b6da

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09364482B2