反应详情

To a solution of N-methoxy-N,2-dimethyl-3-[methyl(2-thienylsulfonyl)amino]-4H-thieno[3,2-b]pyrrole-5-carboxamide (230 mg) in N,N-dimethylformamide (5 mL) was added sodium hydride (60%, oily, 25 mg), and the mixture was stirred at room temperature for 30 min. Chloromethyl methyl ether (51 mg) was added to the reaction mixture, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was dissolved in tetrahydrofuran (5 mL), methyl magnesium bromide (ca. 3.0M diethyl ether solution, 0.4 mL) was added thereto, and the mixture was stirred at room temperature for 30 min. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was dissolved in tetrahydrofuran (5 mL), 6N hydrochloric acid (5.0°mL) was added thereto, and the mixture was stirred at 80° C. overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography to give N-(5-acetyl-2-methyl-4H-thieno[3,2-b]pyrrol-3-yl)-N-methylthiophene-2-sulfonamide (55.2 mg, yield 26%) as gray crystals from a fraction eluted with ethyl acetate-hexane (1:1, volume ratio). melting point 220° C.

1. stirringthe mixture was stirred at room temperature overnight
2. extractionthe mixture was extracted with ethyl acetate
3. washThe ethyl acetate layer was washed with saturated brine
4. dry with materialdried (MgSO4)
5. concentrationconcentrated
6. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
7. additionmethyl magnesium bromide (ca. 3.0M diethyl ether solution, 0.4 mL) was added
8. stirringthe mixture was stirred at room temperature for 30 min
9. additionWater was added to the reaction mixture
10. extractionthe mixture was extracted with ethyl acetate
11. washThe ethyl acetate layer was washed with saturated brine
12. dry with materialdried (MgSO4)
13. concentrationconcentrated
14. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
15. addition6N hydrochloric acid (5.0°mL) was added
16. stirringthe mixture was stirred at 80° C. overnight
17. additionWater was added to the reaction mixture
18. extractionthe mixture was extracted with ethyl acetate
19. washThe ethyl acetate layer was washed with saturated brine
20. dry with materialdried (MgSO4)
21. concentrationconcentrated