反应详情

温度

90 °C

(rac)-1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(7-fluoro-quinolin-6-yl)-ethanol (Stage 174.1, 200 mg, 0.584 mmol) was dissolved in DME (4 mL) under argon atm. 1-[2-(Tetrahydro-pyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (Stage 171.4, 282 mg, 0.875 mmol) was added, followed by 2 M K2CO3 (0.79 mL) and PdCl2(PPh3)2 (20.5 mg, 0.029 mmol). The RM was stirred at 90° C. for 1.5 h. It was then taken into a mixture of EtOAc and 1 M Na2CO3 and extracted. The organic phase was dried on Na2SO4, filtered and evaporation of the solvent. The residue was dissolved in DCM (16 mL), 4 M HCl (dioxane, 0.438 mL, 1.751 mmol) were added at 10° C. The mixture was stirred at rt for 1 h. The solvent was evaporated and the residue was diluted with EtOAc/MeOH (95:5) and washed with 1 M Na2CO3 (1×). The aqueous phases were further extracted with EtOAc (1×). The combined organic layer was dried over Na2SO4, filtered and concentrated. The residue was crystallized in DCM/Et2O to afford the title compound as a slightly yellow solid (tR 2.37 min (conditions 13), MH+=419). 1H-NMR in DMSO-d6: 8.86 (m, 1H), 8.64 (m, 2H), 8.02 (d, 1H), 7.93 (s, 1H), 7.82 (s, 1H), 7.58-7.50 (m, 2H), 7.45-7.40 (m, 2H), 6.25 (s, 1H), 4.86 (t, 1H), 4.00 (m, 2H), 3.60 (m, 2H), 2.15 (s, 3H).

1. extractionextracted
2. customThe organic phase was dried on Na2SO4
3. filtrationfiltered
4. customevaporation of the solvent
5. dissolutionThe residue was dissolved in DCM (16 mL)
6. stirringThe mixture was stirred at rt for 1 h
7. customThe solvent was evaporated
8. additionthe residue was diluted with EtOAc/MeOH (95:5)
9. washwashed with 1 M Na2CO3 (1×)
10. extractionThe aqueous phases were further extracted with EtOAc (1×)
11. dry with materialThe combined organic layer was dried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated
14. customThe residue was crystallized in DCM/Et2O