反应详情

温度

100 °C

A mixture of 2-(5-{12-bromo-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaen-4-yl}-3-methyl-1H-1,2,4-triazol-1-yl)ethan-1-ol (80.0 mg, 0.206 mmol), 1-methyl-4-(pyrrolidin-2-yl)piperidine (41.5 mg, 0.247 mmol), Pd2(dba)3 (9.4 mg, 0.010 mmol), Xphos (9.8 mg, 0.021 mmol), and t-BuONa (59.3 mg, 0.618 mmol) in dioxane (10 ml) was degassed with N2 3 times. The resulting mixture was sealed in a microwave vial and stirred at 100° C. overnight. The solid was filtered off. The filtrate was concentrated to give the crude product, which was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to afford 237 (3.5 mg, 4% yield) as an off white solid. LCMS (ESI): RT=4.03 min, m/z: 478.4 [M+H+]. 1H NMR (500 MHz, MeOD-d4) δ 8.40 (m, 1H), 8.10-8.09 (d, J=8.5 Hz, 1H), 7.56 (s, 1H), 6.44-6.42 (dd, J=9.0, 2.0 Hz, 1H), 6.17 (d, J=2.5 Hz, 1H), 4.68-4.66 (m, 2H), 4.37-4.32 (m, 4H), 3.93-3.91 (t, J=5.5 Hz, 2H), 3.79-3.76 (m, 1H), 3.46-3.37 (m, 3H), 3.17-3.12 (m, 1H), 2.82 (m, 1H), 2.69 (s, 3H), 2.26 (s, 3H), 1.99-1.82 (m, 6H), 1.73-1.70 (m, 1H), 1.56-1.51 (m, 2H), 1.23-1.19 (m, 2H)

1. customwas degassed with N2 3 times
2. customThe resulting mixture was sealed in a microwave vial
3. filtrationThe solid was filtered off
4. concentrationThe filtrate was concentrated
5. customto give the crude product, which
6. customwas purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min)