Dichloromethane → N-(6-(Difluoro(6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide

Participants

Reaction Steps

A mixture of N-(6-((6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (7.2 g, 16.06 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (5.01 g, 24.10 mmol) and PdCl2(dppf):CH2Cl2 (0.655 g, 0.803 mmol) in 1,4-Dioxane:1M Na2CO3 (Ratio: 2.1, Volume: 100 ml) was heated at 95° C. for 4 h. The reaction mixture cooled and concentrated to dryness via rotary evaporation, diluted with EtOAc and water. The resulting solid was collected by filtration, rinsed with H2O followed by EtOAc. The grey color solid dissolved in 20% MeOH in chloroform and treated with activated charcoal for overnight, filtered through a pad of celite and the celite pad rinsed with 20% MeOH in chloroform until no compound detected by HPLC. This solution passed through a silica gel column. The solvent evaporated and the resulting solid rinsed with EtOAc, MeOH, followed by EtOAc and then Et2O, dried under vacuum to provide N-(6-(difluoro(6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (5.13 g, 11.41 mmol, 71.1% yield) as white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.35 (s, 1H), 8.71 (s, 1H), 8.41 (s, 1H), 8.19-8.34 (m, 2H), 8.00-8.12 (m, 2H), 7.91 (dd, J=1.64, 9.47 Hz, 1H), 7.71 (d, J=9.35 Hz, 1H), 3.88 (s, 3H), 1.88-2.02 (m, 1H), 0.83 (d, J=6.32 Hz, 4H). ESI-MS:m/z 450.1 (M+H)+. MP: 274.9° C.

Provenance & Evidence