Reaction Steps
To a 0.166 M solution of crude 3-{3-[2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-benzoyl chloride in methylene chloride (prepared in Example 63, 1.71 mL, 0.28 mmol) was added a 40% solution of methylamine in water (250 μL, 0.32 mmol) and the reaction stirred at 25° C. for 30 min. The solution was diluted with methylene chloride (40 mL), washed with water (2×20 mL), saturated aqueous brine solution (2×20 mL), dried over magnesium sulfate and concentrated in vacuo to an off white foam. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 0% ethyl acetate/methylene chloride to 100% ethyl acetate/methylene chloride) afforded 3-{3-[2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-N-methyl-benzamide (61 mg, 39%) as a white powder: ESI-LRMS m/e calcd for C27H31ClN4O4S [M+] 542.18, found 543.16 [M+H+]; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.04-1.15 (m, 2H, CH2), 1.34-1.79 (m, 8H, 4×CH2), 2.00-2.17 (m, 1H, CH), 2.75 (d, J, 4.5 Hz, 3H, NCH3), 3.32 (s, 3H, SO2CH3), 3.82-3.90 (m, 1H, CH), 5.21 (s, 2H, NCH2), 6.45 (d, J=2.3 Hz, 1H, Ar), 7.28-7.34 (m, 1H, Ar), 7.38 (t, J=7.8 Hz, 1H, Ar), 7.55 (dd, Jo=8.3, Jm=1.6 Hz, 1H, Ar), 7.65 (d, Jm=1.6 Hz, 1H, Ar), 7.67-7.71 (m, 2H, Ar), 7.72 (d, J=2.3 Hz, 1H, Ar), 7.97 (d, Jo=8.3 Hz, 1H, Ar), 8.33-8.45 (brm, 1H, NH), 10.76 (s, 1H, NH).
