Cesium carbonate → 5-chloro-1-[(2,2-difluorocyclopropyl)methyl][1,3]thiazolo[5,4-b]pyridin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

To a round bottom flask was added 5-chloro[1,3]thiazolo[5,4-b]pyridin-2(1H)-one (1-4) (3.5 g, 19 mmol), anhydrous NMP (30 mL), anhydrous 1,4-dioxane (60 mL), cesium carbonate (12 g, 37 mmol), followed by 2-(bromomethyl)-1,1-difluorocyclopropane (3.4 g, 20 mmol). The reaction mixture was then heated to 95° C. while stirring in a hot oil bath for 18 hours. The crude reaction mixture was then cooled to room temperature, then suspended in ethyl acetate and washed with a saturated solution of sodium bicarbonate, followed by water, then brine, dried over sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel chromatography (0-40% EtOAc/Hex) to give 5-chloro-1-[(2,2-difluorocyclopropyl)methyl][1,3]thiazolo[5,4-b]pyridin-2(1H)-one (1-5) as a tan solid. HRMS (M+H)+: observed=277.0008, calculated=277.0008.

Provenance & Evidence