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-(3,4-dichloro-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-(3,4-dichloro-benzyl)-1H-pyrazol-3-yl]-propionamide (133 mg, 79%) as a white solid: ESI-LRMS m/e calcd for C25H26Cl3N3O3S [M+] 553.1, found 554.2 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.03-1.22 (m, 2H, CH2), 1.42-1.90 (m, 8H, 4×CH2), 2.09-2.28 (m, 1H, CH), 3.24 (s, 3 H, SO2CH3), 3.57 (t, J=7.6 Hz, 1H, CH), 5.07 (s, 2H, NCH2), 6.71 (d, J=2.3 Hz, 1H, Ar), 6.95 (dd, Jo=8.2, Jm=2.0 Hz, 1H, Ar), 7.21 (d, Jm=2.0 Hz, 1H, Ar), 7.31 (d, J=2.3 Hz, 1H, Ar), 7.36 (d, Jo=8.2 Hz, 1H, Ar), 7.44 (dd, Jo=8.2, Jm=1.7 Hz, 1H, Ar), 7.58 (d, Jm=1.7 Hz, 1H, Ar), 8.05 (d, Jo=8.2 Hz, 1H, Ar), 8.14 (s, 1H, NH).
