反应详情

To a solution of dimethylsulfone (446 mg) in tetrahydrofuran (10 mL) was added dropwise lithium hexamethyldisilazide (1.6M tetrahydrofuran solution) (2.7 mL) at −78° C., and the mixture was stirred for 1 hr. To the reaction mixture was added dropwise a solution of 6-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridine-3-carbaldehyde (1 g) in tetrahydrofuran (5 mL), and the mixture was stirred for 1 hr. 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 a pale-yellow amorphous solid from a fraction eluted with ethyl acetate-methanol (9:1, volume ratio). The obtained pale-yellow amorphous solid was subjected to basic silica gel column chromatography to give a pale-yellow amorphous solid from a fraction eluted with ethyl acetate-methanol (9:1, volume ratio). The pale-yellow amorphous solid was purified by preparative HPLC to give the title compound (270 mg, yield 22%) as a colorless amorphous solid. MS: 559 (MH+).

1. stirringthe mixture was stirred for 1 hr
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. customto give a pale-yellow amorphous solid from a fraction
7. washeluted with ethyl acetate-methanol (9:1, volume ratio)
8. customto give a pale-yellow amorphous solid from a fraction
9. washeluted with ethyl acetate-methanol (9:1, volume ratio)
10. customThe pale-yellow amorphous solid was purified by preparative HPLC