反应详情

温度

25 °C

To a solution containing {3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-acetic acid (prepared in example 3, 100 mg, 0.22 mmol) in methylene chloride (2 mL), was then added a 2.0 M solution of oxalylchloride in methylene chloride (121 μL, 0.24 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (28 μL, 0.24 mmol) was added to the solution. After 1 h, morpholine (21 μL, 0.24 mmol) was added and the reaction was allowed to proceed for 16 h. The reaction solution was washed with saturated aqueous ammonium chloride solution, the organic phase was concentrated in vacuo and purified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 0% methanol/methylene chloride to 10% methanol/methylene chloride) to afford 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-pyrazol-3-yl]-propionamide (71 mg, 62%) as a white solid: ESI-LRMS m/e calcd for C24H31ClN4O5S [M+] 522.17, found 523.4 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.05-1.18 (m, 2H, CH2), 1.41-1.95 (m, 8H, 4×CH2), 2.15-2.24 (m, 1H, CH), 3.26 (s, 3H, SO2CH3), 3.46 (m, 2H, NCH2), 3.55 (t, J=7.5 Hz, 1H, CH),), 3.58-3.70 (m, 6H, 2×OCH2 and NCH2), 4.81 (s, 2H, NCH2), 6.71 (m, 1H, Ar), 7.34 (m, 1H, Ar), 7.42 (m, 1H, Ar), 7.56 (m, 1H, Ar), 8.04 (d, Jo=8.1 Hz, 1H, Ar), 8.10 (s, 1H, NH).

1. waitAfter 1 h
2. waitto proceed for 16 h
3. washThe reaction solution was washed with saturated aqueous ammonium chloride solution
4. concentrationthe organic phase was concentrated in vacuo
5. custompurified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 0% methanol/methylene chloride to 10% methanol/methylene chloride)