反应详情

温度

50 °C

2-Chloro-5-(2,2-difluoropropyl)-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (707 mg, 2.125 mmol) and 1-cyclopropyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (770 mg, 2.55 mmol) where combined in methyltetrahydrofuran (10 mL) and aqueous sodium carbonate (2 M) (2.2 mL). The reaction mixture was heated in a 50° C. oil bath and then 1,1-bis(di-tert-butylphosphino)ferrocene palladium dichloride (38 mg) was added. The reaction mixture was then placed in an 80° C. oil bath. After about 1 hour the oil bath was reduced to 74° C. After about 4 hours some solvent had evaporated, 6 mL de-gassed methyltetrahydrofuran was added and decreased the oil bath temperature to 70° C. After about 6 hours, solvent had again evaporated, 6 mL de-gassed methyltetrahydrofuran was added. After another hour, 1,1-bis(di-tert-butylphosphino)ferrocene palladium dichloride (9 mg) was added and heating continued at 70° C. for 3 hours, then cooled to room temperature and allowed to stir overnight. The reaction mixture was then diluted with 4 mL 1:1 methyltetrahydrofuran/water, stir for 15 minutes, the solids were collected by filtration, the filter cake washed with 2×3 mL portions of 1:5 water/methyltetrahydrofuran, air-dried for 1 hour, then under vacuum for 1 hour to give the title compound.

1. customwas then placed in an 80° C.
2. customAfter about 4 hours some solvent had evaporated
3. custom6 mL de-gassed methyltetrahydrofuran
4. additionwas added
5. customto 70° C
6. waitAfter about 6 hours
7. customsolvent had again evaporated
8. custom6 mL de-gassed methyltetrahydrofuran
9. additionwas added
10. waitAfter another hour
11. addition1,1-bis(di-tert-butylphosphino)ferrocene palladium dichloride (9 mg) was added
12. temperatureheating
13. waitcontinued at 70° C. for 3 hours
14. temperaturecooled to room temperature
15. additionThe reaction mixture was then diluted with 4 mL 1:1 methyltetrahydrofuran/water
16. stirringstir for 15 minutes
17. filtrationthe solids were collected by filtration
18. washthe filter cake washed with 2×3 mL portions of 1:5 water/methyltetrahydrofuran
19. customair-dried for 1 hour