反应详情

温度

100 °C

To a solution of 4-{4-[6-amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (BB3) (18.3 mg, 0.0391 mmol), trifluoromethanesulfonic acid 5-chloro-6,8-difluoroisoquinolin-3-yl ester (0.0326 mmol), and Pd(PPh3)4 (2.51 mg, 0.00215 mmol) in 1,4-dioxane (0.90 ml) in a sealable microwave tube was added a solution of Cs2CO3 (21.4 mg, 0.0651 mmol) in H2O (0.30 ml). The tube was sealed, evacuated and refilled with nitrogen (3×), and heated in the microwave reactor to 100° C. for 30 min. The reaction mixture was diluted with EtOAc (40 ml), washed with water (2×20 ml) and brine (20 ml), and dried over MgSO4. After concentration in vacuo, a brown oil was obtained. It was then purified by prep. TLC eluting with 4% MeOH/CH2Cl2 to give the title compound as a brown oil. 1H NMR (400 MHz, CDCl3): δ=1.49 (s, 9H), 1.94-2.05 (m, 2H), 2.16-2.24 (m, 2H), 2.87-2.98 (m, 2H), 4.24-4.38 (m, 3H), 6.45 (brs, 2H), 7.18 (t, J=9.6 Hz, 1H), 7.68 (d, J=0.8 Hz, 1H), 7.79 (d, J=0.8 Hz, 1H), 7.99 (d, J=2.4 Hz, 1H), 8.32 (d, J=2.4 Hz, 1H), 8.34 (m, 1H), 9.53 (d, J=1.2 Hz, 1H). MS(ES+): m/z=540.92/542.87 (100/86) [MH+]. HPLC: tR=3.15 min (ZQ3, polar—5 min).

1. customThe tube was sealed
2. customevacuated
3. additionrefilled with nitrogen (3×)
4. additionThe reaction mixture was diluted with EtOAc (40 ml)
5. washwashed with water (2×20 ml) and brine (20 ml)
6. dry with materialdried over MgSO4
7. concentrationAfter concentration in vacuo
8. customa brown oil was obtained
9. customIt was then purified by prep