Cesium carbonate → HCID 178477891, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of cesium carbonate (1.08 g, 3.31 mmol), 2-(azetidin-3-yl)-5-chloro-1H-benzo[d]imidazole dihydrochloride (as described in Preparation 5) (0.23 g, 0.83 mmol), and 2-fluoro-4-(tetrahydro-2H-pyran-4-yl)pyridine (0.15 g, 0.83 mmol) in DMA (1 mL) under argon was heated to 110° C. for 18 h. The mixture was then cooled to RT, ethyl acetate and saturated aqueous ammonium chloride were added and the layers were separated. The organic layer was washed with water (2×), brine, and dried over anhydrous magnesium sulfate. The aqueous layer was then extracted with ethyl acetate (2×) and the combined extracts were washed with water (2×), brine, and added to the original organic layer. The combined organic extracts were filtered and concentrated in vacuo to give an oil that was purified by reversed phase HPLC to give an oil. This oil was partitioned between ethyl acetate and saturated aqueous sodium carbonate solution. The biphasic mixture was stirred vigorously for 30 mins, the layers were separated, and the organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give 5-chloro-2-(1-(4-(tetrahydro-2H-pyran-4-yl)pyridin-2-yl)azetidin-3-yl)-1H-benzo[d]imidazole (0.16 g, 0.43 mmol, 51% yield) as a white solid. [M+1] 369. IC50 (uM) 1.169.

Provenance & Evidence