反应详情

温度

120 °C

7-(3,5-Dimethyl-4-isoxazolyl)-8-(methyloxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one (220 mg, 0.539 mmol) (for a preparation see intermediate 14) was dissolved in POCl3 (2 ml, 21.46 mmol), PCl5 (0.2 g, 0.960 mmol) was added and the mixture was heated at 120° C. for 24 h. The reaction mixture was evaporated in vacuo to give a beige solid. The solid was dissolved in NMP (0.5 ml) and morpholine (0.3 ml, 3.44 mmol) was added, then the solution was heated in the microwave at 150° C. for 1 h. The solution was loaded onto a 20 g SCX-2 cartridge and washed with methanol (30 ml), then eluted with 2M methanolic ammonia (30 ml) and the eluant evaporated in vacuo to give a beige gum. This was dissolved in DCM (3 ml) and loaded onto a 25 g silica column, then eluted with 2M methanolic ammonia/DCM (0-10%, 25 column volumes) and product containing fractions were evaporated in vacuo to give 7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-2-(4-morpholinyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinoline (4.7 mg, 9.84 μmol, 1.827% yield) as a beige solid. LCMS (formate) Rt 0.70 min, MH+ 478

1. customThe reaction mixture was evaporated in vacuo
2. customto give a beige solid
3. temperaturethe solution was heated in the microwave at 150° C. for 1 h
4. washwashed with methanol (30 ml)
5. washeluted with 2M methanolic ammonia (30 ml)
6. customthe eluant evaporated in vacuo
7. customto give a beige gum
8. washeluted with 2M methanolic ammonia/DCM (0-10%, 25 column volumes) and product
9. additioncontaining fractions
10. customwere evaporated in vacuo