反应详情

温度

45 °C

A sealable tube (75 mL) was charged with (R)-6-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (705) (2.00 g, 6.26 mmol), 2-(tert-butylamino)-8-iodo-3-methylquinazolin-4(3H)-one (701) (1.78 g, 5.01 mmol) and K3PO4 (3.98 g, 18.77 mmol) in 1,4-dioxane (16 mL)/water (4 mL). The mixture was bubbled with Argon for 3 min, then XPhos precatalyst II (Sigma-Aldrich; 0.24 g, 0.31 mmol) was added and the tube was sealed and heated in an oil bath at 45° C. for 90 min. The mixture was diluted with EtOAc (80 mL) and water (30 mL) and the layers were separated. The aqueous layer was extracted with EtOAc (100 mL×2). The combined organic layers were dried (MgSO4), filtered and concentrated. The residue was purified on a silica gel column (1-10% MeOH in DCM) to give (R)-2-(tert-butylamino)-3-methyl-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinazolin-4(3H)-one (1.35 g, 3.69 mmol, 59% yield) as a light brown crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.95 (1H, br.), 7.91 (2H, m), 7.62 (1H, s), 7.19 (1H, t, J=7.6 Hz), 6.73 (1H, m), 5.96 (1H, s), 4.54 (1H, q, J=6.4 Hz), 3.49 (3H, s), 1.52 (9H, s), 1.38 (3H, d, J=6.7 Hz). m/z (ESI, +ve ion) 366.2 (M+H)+.

1. customThe mixture was bubbled with Argon for 3 min
2. customthe tube was sealed
3. customthe layers were separated
4. extractionThe aqueous layer was extracted with EtOAc (100 mL×2)
5. dry with materialThe combined organic layers were dried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified on a silica gel column (1-10% MeOH in DCM)