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, allylamine (9 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-allylcarbamoyl-ethyl)-1H-pyrazol-3-yl]-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (9 mg, 16%) as a white solid: ESI-LRMS m/e calcd for C23H29ClN4O4S [M+] 506.19, found 507.34 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.06-1.20 (m, 2H, CH2), 1.42-1.94 (m, 8H, 4×CH2), 2.12-2.30 (m, 1H, CH), 2.65 (t, J=6.3 Hz, 2H, COCH2), 3.26 (s, 3H, SO2CH3), 3.54 (t, J=7.5 Hz, 1H, CH), 3.79-3.84 (m, 2H, CONCH2), 4.31 (t, J=6.3 Hz, 2H, NCH2), 5.02-5.07 (m, 1H, vinylic), 5.06-5.09 (m, 1H, vinylic), 6.55 (brm, 1H, NH), 5.67-5.78 (m, 1H, vinylic), 6.60 (d, J=2.3 Hz, 1H, Ar), 7.30 (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), 8.02 (s, 1H, NH), 8.09 (d, Jo=8.2 Hz, 1H, Ar).
