Sulfuric Acid → N-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-[3-methylisoxazol-5-yl]phenyl)pyridine-3-sulphonamide

Participants

Reaction Steps

n-Butyl lithium (1.63 ml of a 1.6M solution in pentane) was added to a stirred solution of acetone oxime (95 mg) in dry THF (5 ml) at 0° C. After 1 hour a solution of 2-(4-methoxycarbonylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (414 mg) in THF (5 ml) was added. The solution was allowed to warm up over 17 hours. The mixture was poured into a stirred solution of concentrated sulphuric acid (0.6 g) in THF (2.8 ml) and water (0.7 ml) and heated under reflux for 1 hour. The cooled solution was treated with saturated sodium carbonate solution to pH 5 then extracted three times with ethyl acetate. The organic extracts were washed with water and saturated sodium chloride solution then dried (MgSO4). Volatile material was removed by evaporation and the residue was purified by chromatography on a silica gel Mega Bond Elut column, eluting with 0-45% ethyl acetate/hexane to give N-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-[3-methylisoxazol-5-yl]phenyl)pyridine-3-sulphonamide (37 mg) as a solid; 1H NMR (DMSO-d6 at 373 K); 2.2 (s, 3 H), 2.3 (s, 3 H), 3.8 (s, 3 H), 6.7 (s, 1 H), 7.4 (br s, 1 H), 7.5-7.7 (m, 4 H), 7.8 (d, 2 H), 8.5 (dd, 1 H), 8.8 (dd, 1 H); mass spectrum (+ve ESP): 438 (M+H)+.

Provenance & Evidence