反应详情

温度

80 °C

Argon was bubbled into a mixture of Pd2dba3 (Strem, 7.45 mg, 8.13 μmol), Xphos (Strem; 7.75 mg, 0.016 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 (705; 0.085 g, 0.325 mmol), 8-bromo-2-(tert-butylamino)-3-isopropylquinazolin-4(3H)-one (0.055 g, 0.163 mmol), potassium phosphate (0.10 g, 0.488 mmol) in 1 mL dioxane and 0.2 mL water for 1 min. The reaction was sealed and heated to 80° C. for 2 h. The reaction was cooled and transferred to a RBF with some MeOH and adsorbed onto 0.7 g silica gel and dried in vacuo. The material was purified by silica gel chromatography (12 g column) using 0-100% 90/10 DCM/MeOH in DCM. The product-containing fractions were concentrated to afford (R)-2-(tert-butylamino)-3-isopropyl-8-(6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinazolin-4(3H)-one (0.044 g, 0.112 mmol, 69% yield) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.78 (1H, s), 7.84 (2H, ddd, J=14.9, 7.6, 1.6 Hz), 7.59 (1H, s), 7.15 (1H, t, J=7.7 Hz), 6.63 (1H, d, J=1.6 Hz), 5.72 (1H, s), 4.94 (1H, quin, J=6.7 Hz), 4.51 (1H, q, J=6.8 Hz), 3.17 (3H, s), 1.52 (6H, d, J=6.8 Hz), 1.48 (9H, s), 1.36 (3H, d, J=6.7 Hz). m/z (ESI, +ve ion) 394.1 (M+H)+.

1. customThe reaction was sealed
2. temperatureThe reaction was cooled
3. customdried in vacuo
4. customThe material was purified by silica gel chromatography (12 g column)
5. concentrationThe product-containing fractions were concentrated