Reaction Steps
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 (12 μL, 0.14 mmol) was added to the solution at 0° C. After 1 h, propylamine (10 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-propylcarbamoyl-ethyl)-1H-pyrazol-3-yl]-propionamide (18 mg, 33%) as a white solid: ESI-LRMS m/e calcd for C24H33ClN4O4S [M+] 508.2, found 509.5 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 0.84 (t, J=7.4 Hz, 3H, CH3), 1.07-1.22 (m, 2H, CH2), 1.36-1.96 (m, 10H, 5×CH2), 2.18-2.30 (m, 1H, CH), 2.62 (t, J=6.4 Hz, 2H, COCH2), 3.11-3.19 (m, 2H, CONCH2), 3.27 (s, 3H, SO2CH3), 3.56 (t, J=7.6 Hz, 1H, CH), 4.30 (t, J=6.4 Hz, 2H, NCH2), 5.49 (br.t., 1H, NH), 6.58 (d, J=2.3 Hz, 1H, Ar), 7.29 (d, J=2.3 Hz, 1H, Ar), 7.46 (dd, Jo=8.2, Jm=1.7 Hz. 1H, Ar), 7.59 (d, Jm=1.7 Hz, 1H, Ar), 7.93 (s, 1H, NH), 8.08 (d, Jo=8.2 Hz, 1H, Ar).
