Reaction Steps
4-{3-[2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-benzoic acid (prepared in example 45, 100 mg, 0.19 mmol) was suspended in methylene chloride (1 mL) and a 2.0 M solution of oxalyl chloride in methylene chloride (100 μL, 0.20 mmol) was added and the reaction stirred at 25° C. for 10 min. The solution was chilled to 0° C. and 2,6-lutidine (44 μL, 0.38 mmol) was added. The reaction continued to stir at 0° C. for 20 min. Concentrated aqueous ammonium hydroxide (4 drops) was added. The ice bath was removed and the reaction continued to stir at 25° C. for 20 min. The reaction was diluted with ethyl acetate (20 mL), washed with water (2×5 mL), saturated aqueous brine solution (1×5 mL), dried over magnesium sulfate and concentrated in vacuo to a beige foam. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 40% ethyl acetate/hexanes to 100% ethyl acetate/hexanes) afforded 4-{3-[2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-benzamide (49 mg, 49%) as an off white powder: ESI-LRMS m/e calcd for C26H29ClN4O4S [M+] 528.16, found 529.19 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.05-1.20 (m, 2H, CH2), 1.35-1.92 (m, 8H, 4×CH2), 2.11-2.26 (m, 1H, CH), 3.23 (s, 3H, SO2CH3), 3.65 (t, J=7.6 Hz, 1H, CH), 5.18 (s, 2H, NCH2), 6.08 (br.s., 2H, NH2), 6.74 (d, J=2.0 Hz, 1H, Ar), 7.15 (d, Jo=8.1 Hz, 2H, Ar), 7.37 (d, J=2.0 Hz, 1H, Ar), 7.43 (dd, Jo=8.1, Jm=1.6 Hz. 1H, Ar), 7.59 (d, Jm=1.6 Hz, 1H, Ar), 7.72 (d, Jo=8.1 Hz, 2H, Ar), 7.98 (d, Jo=8.1 Hz, 1H, Ar), 8.79 (s, 1H, NH).
