Hydrochloric Acid → N-(3,4-Dimethyl-5-isoxazolyl)-2-[1-(phenylsulfonyl)-1H-indol-3-yl]benzenesulfonamide

Participants

Reaction Steps

A mixture of the title product of Step (D) (350 mg; 0.59 mmol), 6N HCl (6 ml) and EtOH (6 ml) was refluxed for 3 hours. After cooling, the reaction mixture was partitioned between EtOAc (50 ml) and water (25 ml). The aqueous layer was extracted with EtOAc (50 ml) and the combined organic layers were washed with brine (2×50 ml). The blue solution was dried (MgSO4) and concentrated to a dark blue residue. Attempts at purifying this residue using silica gel chromatography were unsuccessful. The material isolated from combining all fractions was subjected to reverse phase preparative HPLC. (30×500 mm ODS column; S-3; two injections-30 and 150 mg; stepwise gradient 75-83% MeOH/H2O+0.1% trifluoroacetic acid (TFA); 2% increments every 5 minutes; 35 ml/minute flow rate.) The pure fractions were concentrated and the residues were partitioned between EtOAc and water. The organic layer was washed with water and brine. Drying (MgSO4), concentration and co-evaporation from MeOH/H2O afforded 130 mg (43%) of the title product of this Example as a light yellow amorphous solid. mp 85-95° C. (dec.); Rf=0.63, EtOAc (UV detection).

Provenance & Evidence