Reaction Steps
4-{3-[2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-benzoic acid (prepared in example 45, 40 mg, 0.08 mmol) was suspended in methylene chloride (1 mL) and a 2.0 M solution of oxalyl chloride in methylene chloride (38 μL, 0.08 mmol) was added and the reaction stirred at 25° C. for 20 min. The solution was chilled to 0° C. and 2,6-lutidine (18 μL, 0.15 mmol) was added. The reaction continued to stir at 0° C. for 20 min. N,N-Di-methyl-3-amino-propyl-amine (12 μL, 0.09 mmol) was added, the ice bath was removed and the reaction continued to stir at 25° C. for 16 h. The reaction was diluted with methylene chloride (10 mL), washed with water (2×4 mL), saturated aqueous brine solution (1×4 mL), dried over magnesium sulfate and concentrated in vacuo to a beige foam. Purification by reverse phase preparative HPLC (Column: Thomson C18 ODSA, 5 micron, 50×21.2 mm ID; 30% acetonitrile/water to 100% acetonitrile/water; 30 mL/min flow rate for 15 min run) followed by flash column chromatography (Merck silica gel 60, 40-63 μm; 0.5% ammonium hydroxide/methanol) afforded 4-{3-[2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-N-(3-dimethylamino-propyl)-benzamide (3 mg, 6.5%) as a clear oil: ESI-LRMS m/e calcd for C31H40ClN5O4S [M+] 613.25, found 614.21 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.08-1.24 (m, 2H, CH2), 1.44-1.94 (m, 8H, 4×CH2), 2.10-2.32 (m, 3H, CH), 2.78 (s, 6H, 2×NCH3), 3.06 (t, J=6.4 Hz, 2H, NCH2), 3.25 (s, 3H, SO2CH3), 3.56-3.66 (m, 2H, CH2), 3.69 (t, J=7.6 Hz, 1H, CH), 5.15 (s, 2H, NCH2), 6.72 (d, J=2.3 Hz, 1H, Ar), 7.13 (d, Jo=8.1 Hz, 2H, Ar), 7.33 (d, J=2.3 Hz, 1H, Ar), 7.49 (dd, Jo=8.1, Jm=1.6 Hz. 1H, Ar), 7.65 (d, Jm=1.6 Hz, 1H, Ar), 7.91 (d, Jo=8.1 Hz, 2H, Ar), 8.05 (d, Jo=8.1 Hz, 1H, Ar), 8.37 (brm, 1H, NH), 8.59 (s, 1H, NH).
