Sodium hydride → N-(4-bromo-3-methyl-5-isoxazolyl)-5-(3-isoxazolyl)thiophene-2-sulfonamide

A solution of 5-amino-4-bromo-3-methylisoxazole (177 mg, 1.0 mmol) in dry THF (2 mL) was added to a suspension of sodium hydride (60% dispersion in mineral oil, 90 mg, 2.2 mmol) in dry THF (1 mL) at 0-5° C. After stirring at 0-5° C. for 5 min, the reaction was warmed to room temperature for 10 min to complete the reaction. The reaction mixture was re-cooled to 0° C., and 5-(3-isoxazolyl)thiophene-2-sulfonyl chloride (273 mg, 1.1 mmol), which had been dissolved in dry THF (2 mL), was added slowly. Stirring was continued for 1 h; during this period the reaction mixture slowly attained ambient temperature. THF was removed under reduced pressure. The residue was dissolved in water (10 mL), the pH was adjusted to 2-3 by adding concentrated HCl, and was extracted with methylene chloride (3×10 ml). The combined organic layers was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give N-(4-bromo-3-methyl-5-isoxazolyl)-5-(3-isoxazolyl)thiophene-2-sulfonamide. The pure material was obtained by recrystallization using hexanes/ethyl acetate (160 mg, 41% yield), m.p. 120-1230 C.

1. temperaturethe reaction was warmed to room temperature for 10 min
2. customthe reaction
3. temperatureThe reaction mixture was re-cooled to 0° C.
4. additionwas added slowly
5. stirringStirring
6. waitwas continued for 1 h
7. waitduring this period the reaction mixture slowly attained ambient temperature
8. customTHF was removed under reduced pressure
9. dissolutionThe residue was dissolved in water (10 mL)
10. additionby adding concentrated HCl
11. extractionwas extracted with methylene chloride (3×10 ml)
12. dry with materialThe combined organic layers was dried over anhydrous magnesium sulfate
13. concentrationconcentrated under reduced pressure

ORD 기록

ord-5935a42f2a1042be90b1f2674b8d4c63

출처 데이터셋

uspto-grants-2001_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06248767B1