Triethylamine → N-(4-bromo-3-methyl-5-isoxazolyl)-2-[N-(3-carboxyphenyl)aminocarbonyl]thiophene-3-sulfonamide

Participants

Reaction Steps

Et3N (2.27 mL, 16. mmol), ethyl 3-aminobenzoate (836 mL, 5.44 mmol) and phosphonitrilic chloride trimer (1.89 g, 5.44 mmol) were sequentially added to a solution of N-(4-bromo-3-methyl-5-isoxazolyl)-2-(carbonyl)thiophene-3-sulfonamide (Example 12) (1 g, 2.27 mmol) in dry THF (20 mL). The reaction was stirred at room temperature for 1 hour and cooled. Water (5 mL) was added to quench the reaction. The resulting solution was concentrated on a rotavap. The residue was diluted with EtOAc and washed with 2N HCl (2×150 mL). The organic layer was dried (MgSO4). The solid was filtered off and the filtrate was concentrated. The residue was treated with 1N NaOH (200 mL) and stirred at 0° C. for 15 minutes. The mixture was then acidified with conc. HCl to pH˜1. The resulting yellow precipitate was filtered off and recrystallized from CH3CN/H2O to give N-(4-bromo-3-methyl-5-isoxazolyl)-2-[N-(3-carboxyphenyl)aminocarbonyl]thiophene-3-sulfonamide (153 mg., 11.6%) as a yellowish powder, m.p. 183-185° C.

Provenance & Evidence