反应详情

温度

130 °C

A mixture of 4-(2,2-dioxido-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazin-9-yl)phenol (300 mg), potassium carbonate (390 mg) and bromocyclobutane (191 mg) in DMSO (5 mL) was stirred at 130° C. for 1 hr. Bromocyclobutane (100 mg) was added, and the mixture was stirred at room temperature overnight. 0.5N Aqueous sodium hydroxide solution, ethyl acetate and THF were added and the mixture was extracted. The extract was washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was separated by HPLC (C18, mobile phase: water/acetonitrile (0.1% TFA containing system)). To the obtained fraction was added a saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was crystallized from acetonitrile, THF and diisopropyl ether to give the title compound (71.9 mg) as a white solid.

1. stirringthe mixture was stirred at room temperature overnight
2. extractionthe mixture was extracted
3. washThe extract was washed with water and saturated brine
4. dry with materialdried over anhydrous sodium sulfate
5. customthe solvent was evaporated under reduced pressure
6. customThe residue was separated by HPLC (C18, mobile phase: water/acetonitrile (0.1% TFA containing system))
7. additionTo the obtained fraction was added a saturated aqueous sodium hydrogen carbonate solution
8. extractionthe mixture was extracted with ethyl acetate
9. dry with materialdried over anhydrous sodium sulfate
10. concentrationconcentrated under reduced pressure
11. customThe residue was crystallized from acetonitrile, THF and diisopropyl ether