反应详情

To a stirred solution of tert-butyl 4-[4-(3-iodo-4-methoxyphenylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylate (82.1 mg, 0.15 mmol), 3-thienylboronic acid (28.8 mg, 0.225 mmol) and potassium carbonate (41.5 mg, 0.3 mmol) in dioxane/water (4:1) (1.0 mL) was added [1,1′-bis(diphenylphosphino)ferrocene]dichloro-palladium(II), complex with dichloromethane (1:1) (12 mg, 0.015 mmol). The resulting mixture was bubbled N2 for 5 min and then heated at reflux for 16 h. After cooled to rt, the solvents were removed under reduced pressure. The residue was dissolved in DMF (2 mL). The DMF solution was filtered and purified by HPLC to give the title compound. 1H-NMR (DMSO-d6, 400 MHz): δ=1.43 (s, 9H), 3.56 (m, 2H), 3.82 (s, 3H), 4.03 (m, 2H), 6.38 (s, br, 1H), 6.73 (s, 1H), 7.09 (d, J=9.2 Hz, 1H), 7.45 (dd, J=0.8, 5.2 Hz, 1H), 7.60 (dd, J=2.8, 4.8 Hz, 1H), 7.76 (m, 1H), 7.80 (dd, J=2.8, 8.8 Hz, 1H), 7.94 (d, J=2.8 Hz, 1H), 8.22 (s, 1H), 9.26 (s, 1H), 11.90 (s, 1H). MS (ES+): m/z 504.05 [MH+]. HPLC: tR=3.22 min (ZQ2000, polar—5 min).

1. customThe resulting mixture was bubbled N2 for 5 min
2. temperatureheated
3. temperatureat reflux for 16 h
4. customthe solvents were removed under reduced pressure
5. dissolutionThe residue was dissolved in DMF (2 mL)
6. filtrationThe DMF solution was filtered
7. custompurified by HPLC