反应详情

温度

0 °C

N-(3-(Aminomethyl)benzyl)-3,5-dichloro-N-((4′-fluorobiphenyl-4-yl)methyl)-2-hydroxybenzenesulfonamide (1.0 g, 1.8 mmol, 1.0 eq) was dissolved in dry methanol. The solution was stirred for 10 minutes and treated with isobutyraldehyde (145 mg, 2 mmol, 1.1 eq). The resulting mixture was stirred for 10 minutes at ambient temperature, refluxed for 3 h, cooled to 0° C. and treated with NaBH4 (210 mg, 5.5 mmol, 3 eq). The mixture was stirred for 30 min at 0° C., quenched by the addition of 10% aq. NaHCO3 solution and stirred for 1 h at ambient temperature. The solvent was evaporated under reduced pressure and ethyl acetate was added. The organic layer was washed with water and dried with anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel (240-280) column chromatography using 10-20% ethyl acetate/hexane as the eluent to afford the desired product (1 g, 90%). 1H NMR (400 MHz, DMSO-d6) δ 0.92-0.94 (s, 6H), 2.0 (t, 1H), 2.67-2.69 (d, 2H), 4.0 (s, 2H), 4.43-4.44 (s, 4H), 7.15-7.16 (d, 2H), 7.22-7.30 (m, 6H), 7.35 (s, 1H), 7.48-7.53 (d, 2H), 7.63-7.64 (d, 1H), 7.65-7.67 (t, 2H). MS (ESI): 602.2 (M+H)+.

1. stirringThe resulting mixture was stirred for 10 minutes at ambient temperature
2. temperaturerefluxed for 3 h
3. stirringThe mixture was stirred for 30 min at 0° C.
4. customquenched by the addition of 10% aq. NaHCO3 solution
5. stirringstirred for 1 h at ambient temperature
6. customThe solvent was evaporated under reduced pressure and ethyl acetate
7. additionwas added
8. washThe organic layer was washed with water
9. dry with materialdried with anhydrous Na2SO4
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by silica gel (240-280) column chromatography