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

Temperature

2.5 °C

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. 120-123° 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 record

ord-7f1a54800d8c4c2cbb98b3239dd60e33

Source dataset

uspto-grants-2004_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06683103B2