Reaction Steps
Argon was bubbled into a mixture of 8-bromo-2-(tert-butylamino)quinazolin-4(3H)-one (408a, 62 mg, 0.21 mmol), K2CO3 (0.116 g, 0.84 mmol), dichlorobis(p-dimethylamino-phenylditbutylphosphine)palladium (ii) (Aldrich; 0.030 g, 0.042 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 (706; 0.110 g, 0.419 mmol) and 2 mL dioxane and 0.4 mL water for 1 min. The reaction was sealed and placed in a 100° C. oil bath for 30 min. The reaction was cooled and partitioned between sat'd aq. NH4Cl and DCM. The aqueous layer was extracted with 5% IPA/CHCl3 three times and the combined organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. This material was dissolved in DMSO, filtered, and purified by RPHPLC, Phenomenex Gemini 150×30 mm C18 column, 10-70% ACN/H2O with 0.1% TFA; product-containing fractions were treated with saturated aqueous NaHCO3 and DCM. The aqueous layer was extracted 3×DCM and combined organics dried over Na2SO4, filtered, and concentrated in vacuo to give 21 mg as a tan solid. The material was sonicated in 0.5 mL DCM for 2 min, then filtered, rinsing 2×DCM. The solid was collected and dried in vacuo to give (R)-2-(tert-butylamino)-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinazolin-4(3H)-one (6 mg, 0.017 mmol, 8% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.21 (1H, br. s.), 10.63 (1H, s), 7.95 (1H, dd, J=7.6, 1.6 Hz), 7.82 (1H, dd, J=7.8, 1.6 Hz), 7.62 (1H, s), 7.16 (1H, t, J=7.7 Hz), 6.79 (1H, d, J=1.4 Hz), 6.30 (1H, s), 4.54 (1H, d, J=6.7 Hz), 1.47 (9H, s), 1.36 (3H, d, J=6.7 Hz). m/z (ESI, +ve ion) 352.1 (M+H)+.
