反应详情

温度

100 °C

To a degassed suspension of 4-(1-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperidin-4-yl)morpholine (84 mg, 0.19 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-amine (52 mg, 0.19 mmol), 2 M Na2CO3 aqueous solution (0.19 mL, 0.38 mmol) in toluene (3 mL) and ethanol (1 mL) was added Pd(PPh3)4 (11 mg, 0.010 mmol). The suspension was then stirred under nitrogen at 100° C. for 18 hours. The reaction mixture was then diluted with EtOAc and water. The aqueous layer was extracted three times with EtOAc. The combined organic extracts were washed with water, dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (25% MeOH in DCM) to give 139 as a white solid (14.3 mg, 14%). LCMS: M+H+=544.3. 1H-NMR (400 MHz, DMSO-d6): δ 9.01 (d, 1H), 8.25 (d, 1H), 8.16 (s, 1H), 7.67 (t, 1H), 7.49 (t, 1H), 7.08 (s, 2H), 4.23 (s, br, 4H), 3.82 (s, 3H), 3.78 (m, 6H), 3.55 (m, 4H), 2.88 (m, 2H), 2.43 (m, 4H), 2.07 (m, 3H), 1.75 (m, 2H), 1.38 (m, 2H)

1. extractionThe aqueous layer was extracted three times with EtOAc
2. washThe combined organic extracts were washed with water
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude product was purified by flash chromatography (25% MeOH in DCM)