Two preparation methods of 1-methyl-2-oxo-4-cyano-1,2-dihydropyridine_Industrial additives

Background and overview of two preparation methods of 1-methyl-2-oxo-4-cyano-1,2-dihydropyridine

1-Methyl-2-oxo-4-cyano-1,2-dihydropyridine is an organic intermediate that can be obtained by methylation of 4-cyano-2(1H)-pyridone Or it can be obtained by dehydration of 1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamide.

Two preparation methods of 1-methyl-2-oxo-4-cyano-1,2-dihydropyridine

Two preparation methods of 1-methyl-2-oxo-4-cyano-1,2-dihydropyridine reported 1.

To a stirred solution of 4-cyano-2(1H)-pyridone (0.25g; 2.08mmol; 1eq) in DMF (5mL) was added sodium hydride (0.12g; 3.12mmol; 1.5eq) and The resulting mixture was stirred at 0°C for 10 minutes. Methyl iodide (0.4 mL; 6.25 mmol; 3 equiv) was then added to the mixture and the resulting mixture was stirred at 23°C for 2 h. The mixture was diluted with water (50 mL) and the organic components were extracted with ethyl propyl acetate (2 x 200 mL). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, filtered and the solvent removed in vacuo to afford the title compound (0.18 g, 67%). 1H NMR (DMSO-d6) δ 7.93 (d, 1H, J=7Hz), 7.00 (s, 1H), 6.52 (dd, 1H, J=2, 7Hz), 3.45 (s, 3H).

Two preparation methods of 1-methyl-2-oxo-4-cyano-1,2-dihydropyridine reported 2.

To 1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamide (7.2 g, 47.3 mmol, Journal of Organic Chemistry, 1959, 24, 196) at about 0°C To a cold solution in DCM (70 mL), TEA (13.19 mL, 95 mmol) and TFAA (8.02 mL, 56.8 mmol) were added. The reaction mixture was stirred at about 0°C for about 2 h. The reaction mixture was filtered and the filtrate was diluted with DCM (100 mL). The organic layer was washed successively with water (2×70 mL) and brine (1×70 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure with bromopyridine to obtain 3.3g (52.0%) of 1-methyl-2-oxo-1,2-dihydropyridine-4-carbonitrile as a white solid. .

References

[1] [China invention, China invention authorization] CN201480075680.1 P2X3 and/or P2X2/3 compounds and methods [Public]/P2X3 and/or P2X2/3 compounds and methods [Authorization]

[2] [Invented in China] CN201280031389.5 Isoxazoline compounds as therapeutic agents