Uses
4,5,6-Trifluoropyrimidine is a starting material for the preparation of O-linked pyrimidinamine-based compounds as deoxycytidine kinase inhibitors. These inhibitors are useful for treatment of cancer.
Synthesis
The general procedure for the synthesis of 4,5,6-trifluoropyrimidine from 4,5,6-trichloropyrimidine was as follows: first, 7160 mL of cyclobutanesulfone and 3876 g of potassium fluoride (KF) were added to an autoclave and stirred for 1 hour at 150 °C. Subsequently, 700 mL of the cyclobutanesulfone was removed by reduced pressure distillation to dry the mixture. The mixture was cooled to 90 °C and the air in the kettle was replaced with nitrogen. Next, a solution of 3122 g of 4,5,6-trichloropyrimidine and 2386 g of dried cyclobutanesulfone preheated to 45 °C was added. The reaction vessel was sealed after the rapid addition of 10 g of CNC catalyst and 20.5 g of nitrobenzene. The mixture was heated to 200 °C and the reaction was stirred for 5 hours, then warmed to 220 °C to continue the reaction for 11 hours. The maximum total pressure was controlled at 6.5 bar during the reaction. Upon completion of the reaction, the mixture was cooled to 40 °C with stirring and the product was slowly depressurized and transferred to an ice-cold receiver. Subsequently, the internal temperature was slowly raised to 150 °C and the product was distilled first at atmospheric pressure and then at reduced pressure. Redistillation of the crude product gave 1540 g of 4,5,6-trifluoropyrimidine (66% of theoretical yield) as a colorless liquid.
