Hydrochloric Acid → 5-(6-Chloropyridazin-3-yl)-6-(2,4-difluorophenyl)imidazo[2,1-b]oxazole

Participants

Reaction Conditions

Reaction Steps

To a flask was added 6-(2,4-difluorophenyl)-5-iodoimidazo[2,1-b]oxazole (10.0 g, 28.9 mmol, Preparation #C.1) and THF (50 mL). The mixture was cooled to about −30° C. and then a solution of iPrMgCl (2.0 M in THF, 15.2 mL, 30.3 mmol) was added dropwise. The reaction mixture was stirred about 15 min at about 0° C. and then a solution of zinc chloride (4.73 g, 34.7 mmol) in THF (50 mL) was added dropwise. The reaction mixture was stirred at about 0° C. for about 30 min. To a second flask was added 3-chloro-6-iodopyridazine (6.67 g, 27.7 mmol, Example #9, Step A) and DMF (20 mL) and the mixture was stirred at ambient temperature until all solids were in solution. To this flask was added Pd(PPh3)4 (1.336 g, 1.156 mmol, Strem) and then the entire contents were poured in to the first reaction flask. The reaction mixture was heated to about 80° C. and stirred for about 1 h. The reaction mixture was cooled to ambient temperature and the solids were filtered. The solid was triturated with 1-propanol (25 mL) to give a solid. The solid was portioned between 1N aqueous HCl (250 mL) and DCM (250 mL). The organic layer was isolated and then extracted with 6N aqueous HCl. The acid layer was then basified with solid Na2CO3 and the precipitate filtered and dried under vacuum to give the title compound (3.26 g, 34%). LC/MS (Table 1, Method a) Rt=2.69 min; MS m/z: 333.1 (M+H)+

Provenance & Evidence