反应详情

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 2 N 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 1 N 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.

1. temperaturecooled
2. customto quench
3. customthe reaction
4. concentrationThe resulting solution was concentrated on a rotavap
5. additionThe residue was diluted with EtOAc
6. washwashed with 2 N HCl (2×150 mL)
7. dry with materialThe organic layer was dried (MgSO4)
8. filtrationThe solid was filtered off
9. concentrationthe filtrate was concentrated
10. additionThe residue was treated with 1 N NaOH (200 mL)
11. stirringstirred at 0° C. for 15 minutes
12. filtrationThe resulting yellow precipitate was filtered off
13. customrecrystallized from CH3CN/H2O