反应详情

Lithium aluminium hydride (5.3 ml, 5.30 mmol, 1M in tetrahydrofuran) was slowly added to {2-(4-Fluoro-phenyl)-2-[4-(1H-pyrazol-4-yl)-phenyl]-ethyl}-carbamic acid benzyl ester (439 mg, 1.06 mmol) in tetrahydrofuran (5 ml) at 0° C. under nitrogen. The reaction mixture was allowed to warm to room temperature, stirred for 51 hours and quenched with water (5 ml), aqueous sodium hydroxide (2N, 5 ml) and ethyl acetate (10 ml). The aqueous layer was separated, extracted with ethyl acetate (2×20 ml). The combined organic liquors were washed with saturated aqueous brine then dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (SiO2), eluting with dichloromethane:methanol:acetic acid:water (120:15:3:2) gradient to (90:18:3:2) to afford the title compound, which was subsequently converted to the hydrochloride salt (100 mg, 32%). LC/MS: (PS-A2) Rt 1.87 [M+H]+ 296. 1H NMR (Me-d3-OD) δ 8.20 (2H, s), 7.57 (2H, d), 7.34-7.29 (4H, m), 7.02 (2H, t), 4.32 (1H, t), 3.67 (2H, d), 2.65 (3H, s).

1. customquenched with water (5 ml), aqueous sodium hydroxide (2N, 5 ml) and ethyl acetate (10 ml)
2. customThe aqueous layer was separated
3. extractionextracted with ethyl acetate (2×20 ml)
4. washThe combined organic liquors were washed with saturated aqueous brine
5. dry with materialthen dried (MgSO4)
6. concentrationconcentrated in vacuo
7. customThe residue was purified by column chromatography (SiO2)
8. washeluting with dichloromethane:methanol:acetic acid:water (120:15:3:2) gradient to (90:18:3:2)