6-(6-(trifluoromethyl)pyridin-2-yl)-1,3,5-triazine-2,4(1H,3H)-dione

108-19-0

155377-05-2

1446507-38-5

1. Methyl 6-(trifluoromethyl)pyridinecarboxylate (50 g, 244 mmol, 1.0 eq.) and urea condensate (30.2 g, 293 mmol, 1.20 eq.) were dissolved in 750 mL of ethanol and stirred for 10-20 min at 30-35 °C. 2. titanium tetraethoxide (Ti(OEt)4, 27.8 g, 122 mmol, 0.5 eq.) was added to the reaction mixture and stirring was continued at 30-35 °C. 3. 350 g of an ethanol solution of 19% wt sodium ethanol (978 mmol, 4.0 eq.) was added slowly and dropwise, then the reaction mixture was heated to 55-65 °C and maintained for 3 hours. 4. Upon completion of the reaction, the reaction mixture was concentrated, cooled to room temperature and diluted with 700 mL of water. 5. pH was adjusted to 1 with concentrated hydrochloric acid solution, 700 mL of dichloromethane (DCM) was added, and the slurry was stirred at 20-30 °C for 5-7 hours. 6. Collect the solid by filtration and wash it sequentially with 6N hydrochloric acid twice, water twice and DCM once. 7. The wet filter cake was dried under vacuum at 50-60 °C to afford 6-(6-(trifluoromethyl)pyridin-2-yl)-1,3,5-triazine-2,4(1H,3H)-dione as a white solid (45.0 g, 174 mmol, 71% yield).