Cesium carbonate → 4-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)-1-methylpyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a mixture of cesium carbonate (563 mg, 1.73 mmol), (1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanone (0.381 g, 1.60 mmol), and 4-(2-fluoropyridin-3-yl)-1-methylpyrrolidin-2-one (0.131 g, 0.675 mmol) was added NMP (2 mL). The reaction mixture was degassed and heated to 140° C. for 11 h. The mixture was cooled to room temperature and diluted with EtOAc and water. The aqueous phase was extracted with EtOAc (4×) and the combined organic extracts were washed with brine (1×), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (20% to 60% EtOAc in hexanes) gave 4-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)-1-methylpyrrolidin-2-one (0.169 g, 0.410 mmol, 61% yield) as an off-white solid. MS m/z: 413.1 (M+1). The mixture of enantiomers was separated by preparatory SFC (Chiralcel OJH (21×250 mm), 25% EtOH/0.2% diethylamine) to afford the individual enantiomers (R)-4-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)-1-methylpyrrolidin-2-one and (S)-4-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)-1-methylpyrrolidin-2-one. MS (ESI, pos. ion) m/z: 413.1 (M+1). IC50 (uM) +++++.

Provenance & Evidence