反应详情

To a solution of sodium bicarbonate (500 mg) and sodium sulfite (353 mg) in 4 ml of water at 0° C. was added portionwise the 7-chlorosulfonyl)-1-oxo-1,2-dihydroisoquinoline-4-carboxylic acid (see Preparation 16) (400 mg). The reaction was warmed to room temperature and then heated at 80° C. for 2 h. The reaction was cooled to 0° C. and acidified to pH-1 with concentrated hydrochloric acid. The suspension was diluted with 4 ml of water and stirred for 15 minutes at 0° C. then filtered under nitrogen. The solid was washed twice with water and was added to a degassed aqueous solution (3 ml) of potassium hydrogen carbonate (280 mg) at 45° C. Ethanol was then slowly added until the solution became slightly cloudy. Iodomethane (262 μl) was then added and the reaction refluxed (45-50° C.) for 5 h. The reaction was concentrated under vacuum, extracted with ethyl acetate and the aqueous phase acidified with concentrated hydrochloric acid. The reaction was stirred at 0° C. for 30 min. and the solid collected by filtration then recrystalised from acetone to yield the title compound as a white solid (325 mg).

1. temperatureheated at 80° C. for 2 h
2. temperatureThe reaction was cooled to 0° C.
3. filtrationthen filtered under nitrogen
4. washThe solid was washed twice with water
5. additionwas added to a degassed aqueous solution (3 ml) of potassium hydrogen carbonate (280 mg) at 45° C
6. additionEthanol was then slowly added until the solution
7. additionIodomethane (262 μl) was then added
8. temperaturethe reaction refluxed (45-50° C.) for 5 h
9. concentrationThe reaction was concentrated under vacuum
10. extractionextracted with ethyl acetate
11. stirringThe reaction was stirred at 0° C. for 30 min.
12. filtrationthe solid collected by filtration
13. customthen recrystalised from acetone