反应详情

温度

40 °C

A mixture of tert-butyl 5-bromo-3-{(1S)-1-[2-chloro-6-(difluoromethoxy)-3-fluorophenyl]-ethyl}-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (10.0 mg, 0.0192 mmol), 1-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (12.9 mg, 0.0385 mmol), Pd(PPh3)4 (1.1 mg, 0.00096 mmol), K2CO3 (7.98 mg, 0.00577 mmol) and 4:1 dioxane:H2O (0.7 mL, 8 mmol) was heated in a microwave reactor at 100° C. for 45 min. 12 M of HCl in H2O (0.04 mL, 0.5 mmol) was added, and the solution was heated to 40° C. for 20 min. The solution was used directly for HPLC purification, and the fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.84 (d, J=7.3 Hz, 3H), 2.04 (s, 3H), 2.17 (s, 3H), 3.50-3.61 (m, 2H), 3.96-4.10 (m, 2H), 4.13-4.19 (m, 1H), 5.07-5.15 (m, 1H), 6.43 (br. s., 1H), 7.12 (dd, J=9.2, 4.4 Hz, 1H), 7.19 (t, J=8.7 Hz, 1H), 7.28 (d, J=1.8 Hz, 1H), 7.41 (d, J=1.3 Hz, 1H), 7.96-8.04 (m, 1H). MS (ES+): m/z=509.15/511.15 (100/50) [MH+]. HPLC: tR=1.33 min (polar—3 min, UPLC-ACQUITY).

1. customThe solution was used directly for HPLC purification
2. additionthe fractions containing the pure product
3. concentrationwere concentrated in vacuo