Potassium Iodide → N-(6-((6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide

Participants

Reaction Conditions

Reaction Steps

To a mixture of 6-((6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)pyridazin-3-amine (21.8 g, 63.9 mmol) and sodium hydrogenphosphate (27.2 g, 192 mmol) in N,N-Dimethylacetamide (250 ml) were added N-(2-bromoacetyl)cyclopropanecarboxamide (19.75 g, 96 mmol) and potassium iodide (10.61 g, 63.9 mmol) at room temperature. The reaction mixture was stirred for 5 h at 100° C. Reaction mixture cooled to room temperature, diluted with EtOAc (1000 ml) and washed with brine solution (5×), dried over Na2SO4, volatiles evaporated and the residue was purified by combiflash (2 to 30% MeOH in dichloromethane over 120 min). Product containing fractions were combined and concentrated to get N-(6-((6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (13.9 g, 31.0 mmol, 48.5% yield) as an off white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.31 (s, 1H), 8.92 (s, 1H), 8.18-8.35 (m, 2H), 7.92-8.06 (m, 1H), 7.61-7.80 (m, 2H), 1.91-2.02 (m, 1H), 0.78-0.89 (m, 4H). ESI-MS:m/z 450.0 (M+2H)+.

Provenance & Evidence