反应详情

温度

55 °C

Borane tetrahydrofuran complex (4.21 mmol) was added dropwise over 2 h to the amide intermediate c (1.24 mmol) in tetrahydrofuran (10 ml) at room temperature under a nitrogen atmosphere. The solution was then stirred at 55° C. for 24 h. The solution was cooled to 0° C. and treated with methanol (2 ml). To this mixture was added concentrated hydrochloric acid (0.5 ml) and the solution heated at 65° C. for 10 h. The solution was then concentrated in vacuo and poured into a 2 N sodium hydroxide solution (10 ml). The aqueous layer was then extracted with ethyl acetate (2×10 ml), the organic layer was dried (MgSO4) and concentrated in vacuo. The resulting residue was applied to silica chromatography gradient eluting with 100% dichloromethane to 10% methanol/dichloromethane to yield intermediate 4-((R)-3-morpholin-4-yl-1-phenylsulfanylmethyl-propylamino)-3-trifluoromethanesulfonyl-benzenesulfonamide, 4-((R)-3-morpholin-4-yl-1-phenylsulfanylmethyl-propylamino)-3-trifluoromethanesulfonyl-benzenesulfonamide as a white solid (76%). 1H NMR (300 MHz, DMSO) δ 7.97 (1H, d, J 2.2 Hz), 7.83 (1H, dd, J 9.2 and 2.3 Hz), 7.35-7.26 (6H, m, ArH), 7.20 (1H, tt, J 7.0 and 1.8 Hz), 7.04 (1H, d, J 9.6 Hz), 6.89 (1H, bd, J 9.1 Hz), 4.12-4.02 (1H, m), 3.49 (4H, bs), 3.37-3.22 (2H, m), 2.33-2.14 (6H, m), 1.94-1.88 (1H, m), 1.76-1.70 (1H, m).

1. temperatureThe solution was cooled to 0° C.
2. temperaturethe solution heated at 65° C. for 10 h
3. concentrationThe solution was then concentrated in vacuo
4. additionpoured into a 2 N sodium hydroxide solution (10 ml)
5. extractionThe aqueous layer was then extracted with ethyl acetate (2×10 ml)
6. dry with materialthe organic layer was dried (MgSO4)
7. concentrationconcentrated in vacuo
8. washeluting with 100% dichloromethane to 10% methanol/dichloromethane