Reaction Steps
To a solution containing {3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-acetic acid (prepared in example 3, 100 mg, 0.22 mmol) in methylene chloride (2 mL), was then added a 2.0 M solution of oxalylchloride in methylene chloride (121 μL, 0.24 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (28 μL, 0.24 mmol) was added to the solution. After 1 h, a 2.0 M solution of methylamine in tetrahydrofuran (121 μL, 0.24 mmol) was added and the reaction was allowed to proceed for 16 h. The reaction solution was washed with saturated aqueous ammonium chloride solution, the organic phase was 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-methylcarbamoylmethyl-1H-pyrazol-3-yl)-propionamide (28 mg, 28%) as a white solid: ESI-LRMS m/e calculated for C21H27ClN4O4S [M+] 466.1, found 467.2 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.03-1.24 (m, 2H, CH2), 1.43-1.97 (m, 8H, 4×CH2), 2.18-2.29 (m, 1H, CH), 2.78 (d, J=4.9 Hz, 3H, NCH3), 3.27 (s, 3H, SO2CH3), 3.60 (t, J=7.5 Hz, 1H, CH), 4.67 (s, 2H, NCH2), 5.83-5.91 (m, 1H, NH), 6.77 (d, J=2.4 Hz, 1H, Ar), 7.33 (d, J=2.4 Hz, 1H, Ar), 7.49 (dd, Jo=8.2, Jm=1.7 Hz, 1H, Ar), 7.62 (d, Jm=1.7 Hz, 1H, Ar), 8.06 (s, 1H, NH), 8.11 (d, Jo=8.2 Hz, 1H, Ar).
