反应详情

Under nitrogen gas, 0.47 ml (6.07 mM) of methane-sulfonyl chloride was added to a solution of 0.62 g (4.02 mM) of 3-(4-fluorophenyl)propanol and 1.1 ml (7.89 mM) of triethylamine in diethyl ether (8 ml) at 0° C. and the mixture was stirred at the prevailing temperature for 1 hour. The reaction was stopped by adding saturated aqueous solution of sodium hydrogen carbonate and the reaction mixture was extracted with diethyl ether. The organic layer was washed with saturated aqueous solution of sodium chloride and dried over MgSO4. The solvent was then distilled off under reduced pressure to recover the crude mesylate. This crude product was not purified but used as it was in the next reaction. To a solution of 0.75 g (2.00 mM) of N-(piperidin-4-yl)-5-thia-1,8b-diazaacenaphthylene-4-carboxamide dihydrochloride and 1.4 ml (10.0 mM) of triethylamine in ethanol (8 ml) was added 0.94 g (<4.02 mM) of the above crude mesylate at room temperature and the mixture was refluxed under nitrogen for 16 hours. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium chloride, dried over MgSO4, and concentrated. The crude product thus obtained was purified by column chromatography (methanol/ethyl acetate 20-30-40%) and recrystallization from ethyl acetate-ethanol to provide the title compound as red-purple crystals.

1. extractionthe reaction mixture was extracted with diethyl ether
2. washThe organic layer was washed with saturated aqueous solution of sodium chloride
3. dry with materialdried over MgSO4
4. distillationThe solvent was then distilled off under reduced pressure
5. customto recover the crude mesylate
6. customThis crude product was not purified
7. customwas in the next reaction
8. temperaturethe mixture was refluxed under nitrogen for 16 hours
9. temperatureAfter cooling
10. extractionextracted with ethyl acetate
11. washThe organic layer was washed with saturated aqueous solution of sodium chloride
12. dry with materialdried over MgSO4
13. concentrationconcentrated
14. customThe crude product thus obtained
15. customwas purified by column chromatography (methanol/ethyl acetate 20-30-40%) and recrystallization from ethyl acetate-ethanol