Hydrochloric Acid → (2R)-5-[4-(2-Hydroxy-4-pyridin-3-ylbutoxy)phenyl]thiophene-2-sulfonic acid amide

Participants

Reaction Conditions

Reaction Steps

2M Aqueous sodium carbonate (2.5 ml), (2R)-4-[2-(tert-butyldimethylsilanyloxy)-4-pyridin-3-yl-butoxy]benzeneboronic acid (Example 7b)), 1.0 g), and tetrakis(triphenylphosphine)palladium(0) (0.1 g) were added to a solution of 5-bromothiophene-2-sulfonic acid amide (1.21 g) in ethanol (25 ml). The mixture was heated at 90° C. for 4 hours. The mixture was cooled to room temperature and solvents were evaporated under reduced pressure. The reaction mixture was triturated with acetone (10 ml) and filtered through a short silica gel column. The column was eluted with a further 10 ml of acetone. The filtrate was evaporated before purification by normal-phase HPLC, eluting with a gradient of 0-10% ethanol in dichloromethane. The oil obtained was dissolved in methanol (25 ml), 2M hydrochloric acid (10 ml) was added and the solution stirred overnight at room temperature. The solid was filtered off, washed with methanol, water, and then diethyl ether. The product was liberated from its hydrochloride salt by stirring in 2M sodium hydrogencarbonate for 30 minutes. The resulting solid was collected by filtration and washed sequentially with water and diethyl ether to afford the title compound as a solid (0.56 g).

Provenance & Evidence