Reaction Steps
2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 410 mg, 1.23 mmol) was suspended in methylene chloride (7 mL) and a 2.0 M solution of oxalyl chloride in methylene chloride (615 μL, 1.23 mmol) was added and the reaction stirred at 25° C. for 15 min. The solution was chilled to 0° C. and 2,6-lutidine (293 μL, 2.46 mmol) was added dropwise. The reaction continued to stir at 0° C. for 15 min. 1-Cyclopropylmethyl-1H-pyrazol-3-ylamine (169 mg, 1.23 mmol) was added as a pre-dissolved reaction in methylene chloride (7 mL), the ice bath was removed and the reaction continued to stir at 25° C. for 25 min. The reaction was diluted with methylene chloride (100 mL), washed with water (2×30 mL), saturated aqueous brine solution (1×20 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; 0% ethyl acetate/methylene chloride to 15% ethyl acetate/methylene chloride) followed by recrystallization from 10% methylene chloride/diethyl ether afforded 2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1-cyclopropylmethyl-1H-pyrazol-3-yl)-propionamide (162 mg, 29%) as a white crystalline solid: ESI-LRMS m/e calcd for C22H28ClN3O3S [M+] 449.15, found 450.19 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 0.32-0.041 (m, 2H, CH2), 0.63-0.70 (m, 2H, CH2), 1.08-1.31 (m, 3H, CH2), 1.44-1.95 (m, 8H, 4×CH2), 2.13-2.37 (m, 1H, CH), 3.28 (s, 3H, SO2CH3), 3.55 (t, J=7.6 Hz, 1H, CH), 3.85 (d, J=7.0 Hz, 2H, NCH2), 6.67 (d, Jo=2.2 Hz, 1H, Ar), 7.38 (d, Jo=2.2 Hz, 1H, Ar), 7.46 (dd, Jo=8.1, Hz, Jm=1.7 Hz. 1H, Ar), 7.60 (d, Jm=1.7 Hz, 1H, Ar), 7.90 (s, 1H, NH), 8.09 (d, Jo=8.1 Hz, 1H, Ar).
