Reaction Steps
To a solution containing 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 100 mg, 0.30 mmol) in methylene chloride (20 mL), was then added a 2.0 M solution of oxalylchloride in methylene chloride (181 μL, 0.36 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (70 μL, 0.61 mmol) was added to the solution at 0° C. After 1 h, crude 1-(4-methyl-benzyl)-1H-pyrazol-3-ylamine (0.42 mmol based on theory) 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-(4-methyl-benzyl)-1H-pyrazol-3-yl]-propionamide (86 mg, 57%) as a white solid: ESI-LRMS m/e calcd for C26H30ClN3O3S [M+] 499.2, found 500.3 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.05-1.19 (m, 2H, CH2), 1.41-1.95 (m, 8H, 4×CH2), 2.10-2.27 (m, 1H, CH), 2.32 (s, 3H, ArCH3), 3.24 (s, 3H, SO2CH3), 3.55 (t, J=7.6 Hz, 1H, CH), 5.07 (s, 2H, NCH2), 6.67 (d, J=2.3 Hz, 1H, Ar), 7.04 (d, Jo=8.1 Hz, 2H, Ar), 7.11 (d, Jo=8.1 Hz, 2H, Ar), 7.26 (d, J=2.3 Hz, 1H, Ar), 7.43 (dd, Jo=8.2, Jm=1.7 Hz, 1H, Ar), 7.57 (d, Jm=1.7 Hz, 1H, Ar), 8.04 (d, Jo=8.2 Hz, 1H, Ar), 8.31 (s, 1H, NH).
