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 (280 mg), trifluoroacetic acid (3.5 mL) and water (10.5 mL) was added concentrated sulfuric acid (3.5 mL), and the mixture was stirred at 60° C. for 3.5 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 tetrahydrofuran (10 mL), thiomorpholine 1-oxide hydrochloride (103 mg) and triethylamine (0.1 mL) were added, and the mixture was stirred at room temperature for 15 min. Sodium triacetoxyborohydride (233 mg) was added, and the mixture was stirred at room temperature for 16 hr. Water was added to the reaction solution, and the 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 residue was silica gel column chromatography (methanol:ethyl acetate=0:100-10:90), and the obtained crude product was further purified by preparative HPLC to give the title compound (56 mg, yield 18%) as a white solid. MS: 581(MH+).

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. stirringthe mixture was stirred at room temperature for 15 min
9. stirringthe mixture was stirred at room temperature for 16 hr
10. extractionthe mixture was extracted with ethyl acetate
11. washThe organic layer was washed with saturated brine
12. dry with materialdried over magnesium sulfate
13. filtrationfiltrated
14. concentrationthe filtrate was concentrated under reduced pressure
15. customthe obtained crude product
16. customwas further purified by preparative HPLC