反应详情

温度

25 °C

To a solution containing 3-{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-propionic acid (prepared in example 9, 50 mg, 0.11 mmol) in methylene chloride (2 mL) was then added a 2.0 M solution of oxalylchloride in methylene chloride (59 μL, 0.12 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (17 μL, 0.14 mmol) was added to the solution at 0° C. After 1 h, 4-(2-aminoethyl) morpholine (15 μL, 0.11 mmol) 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-[2-(2-morpholin-4-yl-ethylcarbamoyl)-ethyl]-1H-pyrazol-3-yl}-propionamide (17 mg, 27%) as a white solid: ESI-LRMS m/e calcd for C27H38ClN5O5S [M+] 579.2, found 580.3 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 0.99-1.11 (m, 2H, CH2), 1.37-1.85 (m, 8H, 4×CH2), 2.05-2.18 (m, 1H, CH), 2.25-2.37 (m, 6H, 3×NCH2), 2.57 (t, J=6.4 Hz, 2H, COCH2), 3.18 (s, 3H, SO2CH3), 3.21 (q, J=5.4 Hz, 2H, CONCH2), 3.47 (t, J=7.5 Hz, 1H, CH), 3.50-3.58 (m, 4H, 2×OCH2), 4.23 (t, J=6.4 Hz, 2H, NCH2), 5.94 (brm, 1, NH), 6.50 (d, J=2.3 Hz, 1H, Ar), 7.22 (d, J=2.3 Hz, 1H, Ar), 7.38 (dd, Jo=8.2, Jm=1.7 Hz. 1H, Ar), 7.51 (d, Jm=1.7 Hz, 1H, Ar), 7.84 (s, 1H, NH), 8.00 (d, Jo=8.2 Hz, 1H, Ar).

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)