反应详情

温度

60 °C

To a mixture of N-[2-[5-(dimethoxymethyl)-4,5-dihydro-1,3-thiazol-2-yl]-5-(2-methoxyethoxy)-1H-indol-7-yl]-N,1-dimethyl-1H-imidazole-2-sulfonamide (335 mg), trifluoroacetic acid (4 mL) and water (12 mL) was added concentrated sulfuric acid (4 mL), and the mixture was stirred at 60° C. for 2 hr. The excess trifluoroacetic acid was evaporated under reduced pressure, and the residue was neutralized with sodium hydrogencarbonate. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and filtrated, and the filtrate was concentrated under reduced pressure. The obtained crude product was dissolved in a mixed solvent of tetrahydrofuran (3 mL) and ethanol (2 mL), and sodium borohydride (26.5 mg) was added under ice-cooling. The reaction solution was stirred at room temperature for 2 hr, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with 1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over magnesium sulfate, and filtrated, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=20:80-90:10), and the obtained crude product was further purified by preparative HPLC to give the title compound (30.8 mg, yield 10%) as a white solid.

1. customThe excess trifluoroacetic acid was evaporated under reduced pressure
2. extractionThe reaction mixture was extracted with ethyl acetate
3. washThe organic layer was washed with saturated brine
4. dry with materialdried over magnesium sulfate
5. filtrationfiltrated
6. concentrationthe filtrate was concentrated under reduced pressure
7. customThe obtained crude product
8. additionwas added under ice-
9. temperaturecooling
10. stirringThe reaction solution was stirred at room temperature for 2 hr
11. extractionthe mixture was extracted with ethyl acetate
12. washThe organic layer was washed successively with 1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine
13. dry with materialdried over magnesium sulfate
14. filtrationfiltrated
15. concentrationthe filtrate was concentrated under reduced pressure
16. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=20:80-90:10)
17. customthe obtained crude product
18. customwas further purified by preparative HPLC