反应详情

温度

30 °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 (60.0 mg, 0.115 mmol), tert-butyl 4-[5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate (58.73 mg, 0.1501 mmol), Pd(PPh3)4 (6.670 mg, 0.005772 mmol), potassium fluoride (20.12 mg, 0.3463 mmol) and 4:1 dioxane:H2O (3 mL, 30 mmol) was heated in a microwave reactor at 100° C. for 30 min. 12 M of HCl in H2O (0.19 mL, 2.3 mmol) was added, and the solution was heated to 30° C. overnight. The organic solvent was removed in vacuo, and the material was extracted with DCM and sat. NaHCO3. The organic layer was concentrated in vacuo and purified via column chromatography, eluting with 3-8% (7N NH3 in MeOH)/DCM. The fractions containing the pure product were concentrated in vacuo to afford the title compound as white solid. 1H NMR (400 MHz, CD3OD): δ=1.84 (d, J=7.3 Hz, 3H), 1.87-1.96 (m, 2H), 2.00-2.12 (m, 2H), 2.23 (s, 3H), 2.72-2.82 (m, 2H), 3.15-3.23 (m, 2H), 4.31 (tt, J=11.6, 3.9 Hz, 1H), 5.11 (q, J=7.3 Hz, 1H), 6.43 (br. s., 1H), 7.12 (dd, J=9.0, 4.7 Hz, 1H), 7.18 (t, J=8.7 Hz, 1H), 7.38 (d, J=1.8 Hz, 1H), 7.39 (d, J=1.3 Hz, 1H), 7.48 (s, 1H), 8.13 (d, J=2.0 Hz, 1H). MS (ES+): m/z=504.15/506.16 (100/50) [MH+]. HPLC: tR=1.15 min (polar—3 min, UPLC-ACQUITY).

1. customThe organic solvent was removed in vacuo
2. extractionthe material was extracted with DCM and sat. NaHCO3
3. concentrationThe organic layer was concentrated in vacuo
4. custompurified via column chromatography
5. washeluting with 3-8% (7N NH3 in MeOH)/DCM
6. additionThe fractions containing the pure product
7. concentrationwere concentrated in vacuo