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, 0.15 mmol) was added to the solution at 0° C. After 1 h, benzylamine (12 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 N-[1-(2-benzylcarbamoyl-ethyl)-1H-pyrazol-3-yl]-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (19 mg, 32%) as a white solid: ESI-LRMS m/e calcd for C28H33ClN4O4S [M+] 556.2, found 557.4 [M+H+]; 1H NMR (400 MHz, CDCl3), δ ppm 1.04-1.22 (m, 2H, CH2), 1.42-1.93 (m, 8H, 4×CH2), 2.13-2.29 (m, 1H, CH), 2.67 (t, J=6.2 Hz, 2H, COCH2), 3.25 (s, 3H, SO2CH3), 3.52 (t, J=7.6 Hz, 1H, CH), 4.31 (t, J=6.2 Hz, 2H, NCH2), 4.36 (d, J=5.5 Hz, 2H, NCH2Ar), 5.91 (t, J=5.5 Hz, 1H, NH), 6.60 (d, J=2.3 Hz, 1H, Ar), 7.06-7.13 (m, 2H, Ar), 7.21-7.26 (m, 3H, Ar), 7.28 (d, J=2.3 Hz, 1H, Ar), 7.44 (dd, Jo=8.2, Jm=1.7 Hz. 1H, Ar), 7.58 (d, Jm=1.7 Hz, 1 h, Ar), 8.67 (s, 1H, NH), 8.06 (d, Jo=8.2 Hz, 1H, Ar).
