反应详情

温度

25 °C

To a solution containing 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 100 mg, 0.30 mmol) in methylene chloride (20 mL), was then added a 2.0 M solution of oxalylchloride in methylene chloride (166 μL, 0.33 mmol) at 0+ C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (46 μL, 0.39 mmol) was added to the solution at 0° C. After 1 h, 1-(4-methanesulfonyl-benzyl)-1H-pyrazol-3-ylamine (0.30 mmol based on theory) was added and the reaction was allowed to proceed for 16 h. The reaction solution was washed with 1.0 M aqueous hydrochloric acid solution, dried over sodium sulfate, 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-(4-methanesulfonyl-benzyl)-1H-pyrazol-3-yl]-propionamide (150 mg, 88%) as a white solid: ESI-LRMS m/e calcd for C26H30ClN3O5S2 [M+] 563.13, found 564.5 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.03-1.21 (m, 2H, CH2), 1.34-1.88 (m, 8H, 4×CH2), 2.09-2.29 (m, 1H, CH), 2.98 (s, 3 H, SO2CH3), 3.22 (s, 3H, SO2CH3), 3.56 (t, J=7.5 Hz, 1H, CH), 5.24 (AB, Jgem=15.9 Hz, 2H, NCH2), 6.76 (d, J=2.3 Hz, 1H, Ar), 7.14 (d, Jo=8.3 Hz, 2H, Ar), 7.38 (dd, Jo=8.2, Jm=1.7 Hz. 1H, Ar), 7.44 (d, J=2.3 Hz, 1H, Ar), 7.53 (d, Jm=1.7 Hz, 1H, Ar), 7.75 (d, Jo=8.3 Hz, 2H, Ar), 7.91 (d, Jo=8.2 Hz, 1H, Ar), 8.34 (s, 1H, NH).

1. waitAfter 1 h
2. waitto proceed for 16 h
3. washThe reaction solution was washed with 1.0 M aqueous hydrochloric acid solution
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated in vacuo
6. custompurified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 0% methanol/methylene chloride to 10% methanol/methylene chloride)