Hydrochloric Acid → (Rac)-1-(7-fluoro-quinolin-6-yl)-1-{6-[1-(2-hydroxy-ethyl)-1h-pyrazol-4-yl]-imidazo[1,2-b]pyridazin-3-yl}-ethanol

Participants

Reaction Conditions

Reaction Steps

(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).

Provenance & Evidence