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 (17 μL, 0.14 mmol) was added to the solution at 0° C. After 1 h, methanol (20 μL, 0.49 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 3-{3-[2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-propionic acid methyl ester (28 mg, 55%) as a white solid: ESI-LRMS m/e calcd for C22H28ClN3O5S [M+] 481.1, found 482.5 [M+H+]; 1H NMR (400 MHz, CDCl3), δ ppm 1.08-1.21 (m, 2H, CH2), 1.40-1.95 (m, 8H, 4×CH2), 2.13-2.28 (m, 1H, CH), 2.82 (t, J=6.5 Hz, 2H, COCH2), 3.26 (s, 3H, SO2CH3), 3.54 (t, J=7.6 Hz, 1H, CH), 3.67 (s, 3 H, CO2CH3), 4.27 (t, J=6.5 Hz, 2H, NCH2), 6.62 (d, J=2.3 Hz, 1H, Ar), 7.30 (d, J=2.3 Hz, 1H, Ar), 7.45 (dd, Jo=8.2, Jm=1.7 Hz. 1H, Ar), 7.59 (d, Jm=1.7 Hz, 1H, Ar), 7.89 (s, 1H, NH), 8.08 (d, Jo=8.2 Hz, 1H, Ar).
