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, the crude 1-phenethyl-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-phenethyl-1H-pyrazol-3-yl)-propionamide (135 mg, 89%) as a white solid: ESI-LRMS m/e calcd for C26H30ClN3O3S [M+] 499.2, found 500.4 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.06-1.23 (m, 2H, CH2), 1.39-1.93 (m, 8H, 4×CH2), 2.09-2.33 (m, 1H, CH), 3.05 (t, J=7.2 Hz, 2H, ArCH2), 3.26 (s, 3H, SO2CH3), 3.60 (t, J=7.6 Hz, 1H, CH), 4.16 (t, J=7.2 Hz, 2H, NCH2), 6.58 (d, J=2.2 Hz, 1H, Ar), 7.00-7.05 (m, 3H, Ar), 7.16-7.29 (m, 3H, Ar), 7.47 (dd, Jo=8.1, Jm=1.6 Hz, 1H, Ar), 7.61 (d, Jm=1.6 Hz, 1H, Ar), 8.06 (d, Jo=8.1 Hz, 1H, Ar), 8.63 (s, 1H, NH).
