2-methyl-2-(3-methyl-4-nitro-1H-pyrazol-1-yl)propanamide synthesis

Yield:1374829-43-2 92%

Reaction Conditions:

with ammonia in methanol at -20 - 25; for 16 h;Large scale;

Steps:

1

Methanol (23 L) and 2-methyl-2-(3-methyl-4-nitro-lif-pyrazol-l-yl)propanoate 3a (2.25 kg, 1.0 equiv) were charged into a 50-L reactor and cooled to approximately -20 °C. Ammonia gas was purged over a period of 5 h and then the reaction mixture warmed to 25 °C. After 16 h, the reaction mixture was concentrated under reduced pressure (~50 °C) to give the crude product. Ethyl acetate (23 L) was charged and the solution agitated in the presence of charcoal (0.1 w/w) and Celite (0.1 w/w) at 45 °C. The mixture was filtered and concentrated under reduced pressure, and then the solid was slurried in methyl tert-butyl ether (MTBE, 11.3 L) at RT for 2 h. Filtration and drying at ~45 °C gave 2-m ethyl -2-(3 -m ethyl -4-ni tro- 1 //-pyrazol - 1 - yl)propanamide 4a (1.94 kg, >99% purity by HPLC, 92% yield).

References:

WO2019/126383,2019,A1 Location in patent:Page/Page column 14; 15