反应详情

温度

50 °C

6-Methyl-5-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxylic acid (52.0 kg, 1 mol eq, limiting reagent) and acetonitrile (208 L, 4 rel vol,) were charged. The reaction mixture was heated to 50° C. 1,1′-s carbonyldiimidazole as a solution in acetonitrile (208 L, 4 rel vol) is charged to the reaction until the reaction is complete as judged by HPLC. C-(5-(Methanesulfonyl)pyridine-2-yl)methylamine monohydrochloride (33.8 kg, 1.1 mol eq) was charged and the reaction maintained at 50° C. until the reaction was deemed complete as judged by HPLC. Water (780 L, 15 rel vol) was charged. The reaction mixture was stirred, cooled and further stirred. The solid was collected by filtration and washed twice with water (2×104 L, 2×2 rel vol) and dried to constant weight to yield the title compound (96.0 kg, 176.0 mol, 96%); 1H NMR (d6-DMSO): δ 1.83 (s, 3H); 3.29 (s, 3H); 3.72 (s, 3H); 4.73 (d, 2H, J 5.8 Hz); 6.33 (d, 1H, J=1.9 Hz); 7.53 (d, 1H, J=1.9 Hz); 7.57 (d, 1H, J 8.3 Hz); 7.81-7.88 (m, 2H); 7.92-7.94 (m, 1H); 8.03 (s, 1H); 8.21 (s, 1H); 8.27 (dd, 1H, J 2.3, 7.9 Hz); 8.99 (d, 1H, J=2.3 Hz); 10.06 (t, 1H, J 6.0 Hz); LCMS: m/z 546.3 (MH+).

1. additionwere charged
2. temperaturethe reaction maintained at 50° C. until the reaction
3. temperaturecooled
4. stirringfurther stirred
5. filtrationThe solid was collected by filtration
6. washwashed twice with water (2×104 L, 2×2 rel vol)
7. customdried to constant weight