反应详情

温度

25 °C

In a flask containing N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-furan-3-yl)-propionamide (138 mg, 0.25 mmol) was added ethanol (6 ml) and concentrated hydrochloric acid (5 drops) and was stirred at 25° C. for 2 h. The reaction was then concentrated in vacuo to remove the ethanol, diluted with ethyl acetate (50 ml) and washed with a saturated aqueous sodium bicarbonate solution. The organic layer was then dried over magnesium sulfate, filtered and concentrated in vacuo. Purification on an AnaLogix Intelliflash system (12 g column, 5% methanol/ethyl acetate) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-(tetrahydro-furan-3-yl)-propionamide (76 mg, 69%) as an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 1.45-1.57 (m, 1H, CH of CH2), 1.68-1.84 (m, 1H, CH of CH2), 1.88-2.02 (m, 2 H, 2×CH of 2×CH2), 2.06-2.22 (m, 1H, CH), 3.22-3.30 (m, 1H, OCH of OCH2), 3.31 (s, 3H, SO2CH3), 3.53-3.77 (m, 5H, ArCH, SiOCH2, and 2×OCH of 2×OCH2), 3.83-3.93 (m, 1H, OCH of OCH2), 3.97-4.02 (m, 2H, NCH2), 4.82 (t, J=5.4 Hz, 1H, OH), 6.42 (d, J=2.2 Hz, 1H, Ar), 7.54 (d, J=2.2 Hz, 1H, Ar), 7.60 (2×dd, Jo=8.3 Hz, Jm=1.7 Hz, 1H, Ar), 7.71, 7.72 (2×d, Jm=1.7 Hz, 1H, Ar), 8.01 (d, Jo=8.3 Hz, 1H, Ar), 10.81, 10.82 (2×s, 1H, NH).

1. concentrationThe reaction was then concentrated in vacuo
2. customto remove the ethanol
3. additiondiluted with ethyl acetate (50 ml)
4. washwashed with a saturated aqueous sodium bicarbonate solution
5. dry with materialThe organic layer was then dried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customPurification on an AnaLogix Intelliflash system (12 g column, 5% methanol/ethyl acetate)