反应详情

温度

60 °C

The 2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1H-pyrazol-3-yl)-propionamide (prepared in example 2, 115 mg, 0.29 mmol) was dissolved in anhydrous N,N-dimethylformamide (2 mL) and warmed to 60° C. in a sealed vial. Methyl-isocyanate (165 mg, 2.90 mmol) was transferred via syringe to the pyrazole solution. The mixture was heated at 60° C. for 2 h while stirring in the sealed vial. The mixture was diluted with ethyl acetate (25 mL), washed with water (2×15 mL), saturated aqueous brine solution (15 mL), dried over magnesium sulfate and concentrated in vacuo. Purification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 15% ethyl acetate/hexanes to 100% ethyl acetate/hexanes) afforded 3-[2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazole-1-carboxylic acid methylamide (18 mg, 14%) as a white powder: ESI-LRMS m/e calcd for C20H25ClN4O4S [M+] 452.1, found 453.2 [M+H+], 395.9 [M−CONCH3+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.04-1.23 (m, 2H, CH2), 1.43-1.97 (m, 8H, 4×CH2), 2.11-2.34 (m, 1H, CH), 2.95 (d, J=4.6 Hz, 3H, NCH3), 3.27 (s, 3H, SO2CH3), 3.65 (t, J=7.5 Hz, 1H, CH), 6.81 (q, J=4.6 Hz, 1H, NH), 6.84 (d, J=2.7 Hz, 1H, Ar), 7.46 (dd, Jo=8.2, Jm=1.7 Hz, 1H, Ar), 7.60 (d, Jm=1.7 Hz, 1H, Ar), 8.04 (d, Jo=8.2 Hz, 1 H, Ar), 8.07 (d, J=2.7 Hz, 1H, Ar), 8.32 (s, 1H, NH).

1. temperatureThe mixture was heated at 60° C. for 2 h
2. washwashed with water (2×15 mL), saturated aqueous brine solution (15 mL)
3. dry with materialdried over magnesium sulfate
4. concentrationconcentrated in vacuo
5. customPurification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 15% ethyl acetate/hexanes to 100% ethyl acetate/hexanes)