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 aminomethyl cyclopropane (20 mg, 0.28 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-cyclopropylmethyl-benzamide (60 mg, 36%) as a white powder: ESI-LRMS m/e calcd for C30H35ClN4O4S [M+] 582.21, found 583.33 [M+H+]; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.17-0.27 (m, 2H, CH2), 0.39-0.046 (m, 2H, CH2), 0.98-1.17 (m, 3H, CH and CH2), 1.37-1.78 (m, 8H, 4×CH2), 2.02-2.17 (m, 1H, CH), 3.12 (t, J=6.0 Hz, 2H, NCH2), 3.32 (s, 3H, SO2CH3), 3.83-3.91 (m, 1H, CH), 5.22 (s, 2H, NCH2), 6.46 (d, J=2.0 Hz, 1H, Ar), 7.28-7.36 (m, 1H, Ar), 7.39 (t, J=8.0 Hz, 1H, Ar), 7.56 (d, Jo=7.8 Hz, 1H, Ar), 7.65 (d, Jm=1.2 Hz, 1H, Ar), 7.69-7.80 (m, 3H, Ar), 7.97 (d, Jo=8.2 Hz, 1H, Ar), 8.51 (m, 1H, NH), 10.77 (s, 1H, NH).
