反应详情

温度

70 °C

Combine 2-amino-5-fluoro-4-chloro-1-methyl-6-oxo-1,6-dihydropyridine-carbonitrile (33.0 g, 0.164 mol) and 99% formic acid (264 mL, 8 volumes) in a dried vessel. Heat to 70° C. When a solution is formed, add concentrated aqueous hydrochloric acid (165 mL, 5 volumes). After 20 hours, add another portion of concentrated aqueous hydrochloric acid (35 mL) and heated at 70° C. for another 4 h. Then cool the reaction mixture to the ambient temperature and add ice-water (350 mL, 10 volumes). Cool in an ice bath to give a solid. After 30 minutes, collect the solid by filtration, rinse with water (2×30 mL), and dry in vacuo to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ12.96 (s, 1H), 8.35 (s, 1H). 3.61 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ157.7 (d, J=4.4 Hz), 154.6 (d, J=26.4 Hz), 151.2 (d, J=2.2 Hz), 149.9, 146.4 (d, J=242 Hz), 125.0 (d, J=16.9 Hz), 99.94, 29.8; 19F NMR (376 MHz, DMSO-d6) δ−133.8; MS (M+H)+m/z calcd 230.0. found 230.0.

1. customWhen a solution is formed
2. temperatureheated at 70° C. for another 4 h
3. temperatureThen cool the reaction mixture to the ambient temperature
4. temperatureCool in an ice bath
5. customto give a solid
6. waitAfter 30 minutes
7. customcollect the solid
8. filtrationby filtration
9. washrinse with water (2×30 mL)
10. customdry in vacuo