反应详情

温度

5 °C

A mixture of 2.9 kg 6-hydroxy-5-methyl-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one, 4.6 kg of diisopropylethylamine and 17.0 kg of THF was cooled to 0-10° C., then treated with 2.6 kg pivaloyl chloride at a rate to maintain the temperature <20° C. The mixture was stirred until the reaction was complete by HPLC, then 17.8 kg of toluene was added, followed by 20.6 kg of 15% aqueous potassium dihydrogen phosphate solution. The phases were separated and the organic was washed with 10.2 kg water. The organic phase was filtered, then distilled under vacuum with a maximum temperature of 65° C. Additional toluene can be added and distillation continued until the concentration of THF was <8%, and the total reactor volume was reduced to 31 L. The resulting slurry was cooled to 20-25° C. and treated with 20.3 kg heptane over 1.5 h. The slurry was cooled to 0-5° C. and held for 1 h, then the solid was collected by filtration and dried to yield 4.0 kg of 2,2-dimethyl-propionic acid 5-methyl-4-oxo-3,4-dihydro-pyrrolo[2,1-f][1,2,4]triazin-6-yl ester with a purity of 95-99%.

1. temperatureto maintain the temperature <20° C
2. customThe phases were separated
3. washthe organic was washed with 10.2 kg water
4. filtrationThe organic phase was filtered
5. distillationdistilled under vacuum with a maximum temperature of 65° C
6. additionAdditional toluene can be added
7. distillationdistillation
8. temperatureThe resulting slurry was cooled to 20-25° C.
9. additiontreated with 20.3 kg heptane over 1.5 h
10. temperatureThe slurry was cooled to 0-5° C.
11. filtrationthe solid was collected by filtration
12. customdried