Reaction Steps
A solution of 8-bromo-2-(tert-butylamino)-3-cyclobutylquinazolin-4(3H)-one (254.1 mg, 0.725 mmol), (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 (Example 705; 238 mg, 0.907 mmol), potassium phosphate (462 mg, 2.176 mmol), and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (XPhos precatalyst, 2nd generation; Aldrich; 28.6 mg, 0.036 mmol) in a mixture of 1,4-dioxane (3.0 mL) and water (0.750 mL) was stirred under argon at 45° C. for 1 h. The reaction mixture was then concentrated onto silica gel and chromatographically purified (silica gel, 50-100% EtOAc/hexanes, then 0-10% MeOH/DCM) to provide (R)-2-(tert-butylamino)-3-cyclobutyl-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinazolin-4(3H)-one (206.3 mg, 0.509 mmol, 70% yield) as a white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.95 (1H, s), 7.87 (1H, dd, J=7.7, 0.9 Hz), 7.80 (1H, dd, J=7.7, 0.9 Hz), 7.61 (1H, s), 7.13 (1H, t, J=7.7 Hz), 6.72 (1H, s), 5.81 (1H, s), 4.48-4.64 (2H, m), 2.63 (2H, td, J=11.3, 5.0 Hz), 2.01-2.18 (2H, m), 1.56-1.70 (2H, m), 1.48 (9H, s), 1.36 (3H, d, J=6.7 Hz). m/z (ESI, +ve) 406.0 (M+H)+.
