反应详情

To a stirred solution of (±)-2a,5-dihydropyrrolo[4,3,2-de]quinoline-2,4(1H,3H)-dione (2.00 g, 10.6 mmol, described in Intermediate 18) in degassed DMF (30 mL) at 0° C. was added sodium hydride (468 mg of a 60% dispersion in mineral oil, 11.7 mmol). The mixture was stirred for 10 min, then N-(bromomethyl)phthalimide (2.55 g, 10.6 mmol) was added and stirring was continued for 2 h. An additional portion of N-(bromomethyl)phthalimide (500 mg) was added and stirring was continued for 1 h. The reaction mixture was quenched with saturated aqueous NaHCO3 (100 mL) and extracted with EtOAc (3×50 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH—100:0 to 90:10, to give the title compound. MS: m/z=348 (M+1).

1. stirringstirring
2. waitwas continued for 2 h
3. stirringstirring
4. waitwas continued for 1 h
5. customThe reaction mixture was quenched with saturated aqueous NaHCO3 (100 mL)
6. extractionextracted with EtOAc (3×50 mL)
7. dry with materialThe combined organic extracts were dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude product was purified by silica gel chromatography
11. washeluting with a gradient of CH2Cl2