反应详情

温度

80 °C

To a solution of 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazolin-7-ol (2.5 g) in 1-methyl-2-pyrrolidinone (25 ml) and methyl tert-butyl ether (1.8 ml) was added potassium carbonate (815 mg). The mixture was degassed by holding under vacuum and letting down with nitrogen. This was carried out five times. The mixture was heated to 80° C. and 4-azoniaspiro[3,4]octane bromide (1.75 g) was added. The mixture was maintained at 80° C. for 3.5 hours. To the hot mixture was added water (27 ml) over 2 hours. The mixture was cooled to 64° C. and the solid filtered. The solid was washed with 1:1 v/v 1-methyl-2-pyrrolidinone/water (5 ml) and then water (4×5 ml). The solid was dried in a vacuum oven to give 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline.

1. customThe mixture was degassed
2. addition4-azoniaspiro[3,4]octane bromide (1.75 g) was added
3. temperatureThe mixture was maintained at 80° C. for 3.5 hours
4. additionTo the hot mixture was added water (27 ml) over 2 hours
5. temperatureThe mixture was cooled to 64° C.
6. filtrationthe solid filtered
7. washThe solid was washed with 1:1 v/v 1-methyl-2-pyrrolidinone/water (5 ml)
8. customThe solid was dried in a vacuum oven