反应详情

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 (41.1 mg, 0.0791 mmol), 1-(5,8-dioxaspiro[3.4]oct-2-yl)-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (38.0 mg, 0.119 mmol), Pd(PPh3)4 (4.57 mg, 0.00396 mmol), K2CO3 (32.8 mg, 0.237 mmol) and 4:1 dioxane:H2O (3 mL, 30 mmol) was heated to 95° C. for 1 h. The solution was allowed to cool to rt, and 2 M of HCl in H2O (2 mL, 4 mmol) was added. The mixture was heated at 45° C. overnight. The organic solvent was removed in vacuo, and the material was extracted with DCM and sat. NaHCO3. The organic layer was loaded onto silica gel for column chromatography, eluting with 1-3% MeOH/DCM. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. MS (ES+): m/z=489.09/491.09 (100/50) [MH+]. HPLC: tR=4.04 min (polar—5 min, ZQ3).

1. temperatureThe mixture was heated at 45° C. overnight
2. customThe organic solvent was removed in vacuo
3. extractionthe material was extracted with DCM and sat. NaHCO3
4. washeluting with 1-3% MeOH/DCM
5. additionThe fractions containing the pure product
6. concentrationwere concentrated in vacuo