1-(2-Amino-3,5-dimethylphenyl)ethan-1-one → N-(2-acetyl-4,6-dimethylphenyl)-3-(((4-chloro-3-methyl-5-isoxazolyl)amino)sulfonyl)-2-thiophenecarboxamide

Participants

Reaction Steps

To a solution of 2′-amino-3′,5′-dimethylacetophenone (1.9 g, 11.66 mmol) in dichloromethane (20 mL) at room temperature was added N-(4-chloro-3-methyl-5-isoxazolyl)-N-methoxymethyl-3-sulfamoyl-2-thiophenecarbonyl chloride (Example 51) (1 g, 2.86 mmol). The mixture was stirred for 10 h during which much yellow precipitate formed. The reaction was then concentrated and the residue was diluted with ethyl acetate (50 mL) and washed with 1 N HCl (50 mL). The organic layer was concentrated and the residue was dissolved in methanol (30 mL) followed by the addition of concentrated HCl (15 mL). The mixture was then heated under reflux for 2 h before it was cooled to room temperature, diluted with ethyl acetate (200 mL) and washed with water (2×200 mL). The organic layer was separated, dried (MgSO4), the solids filtered and the filtrate concentrated. The residue was then purified by reverse phase HPLC to give N-(2-acetyl-4,6-dimethylphenyl)-3-(((4-chloro-3-methyl-5-isoxazolyl)amino)sulfonyl)-2-thiophenecarboxamide (580 mg, 43%).

Provenance & Evidence