Reaction Steps
To a stirred solution of (R)-3-cyclopentyl-2-(3-methylsulfonyl-phenyl)-propionic acid (200 mg, 0.65 mmol) in benzene (10 mL) was added oxalyl chloride (123 mg, 0.97 mmol) and DMF (1 drop) and the reaction was stirred at 25° C. for 1 h. The reaction was concentrated under reduced pressure and the residue was dissolved into methylene chloride (10 mL) under a nitrogen atmosphere. To this stirred solution was added N,N′-diisopropylethylamine (125 mg, 0.97 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared as in Example 80, 130 mg, 0.84 mmol). The reaction was stirred at 25° C. for 18 h and then diluted with methylene chloride (30 mL). The methylene chloride was washed with water, 2 N aqueous hydrochloric acid solution, saturated sodium bicarbonate and saturated sodium chloride solution and then dried over magnesium sulfate. Filtration and concentration afforded the crude product which was purified by flash column chromatography (Biotage 40S Flash Column; 80% ethyl acetate/hexanes) to yield (R)-3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(3-methanesulfonyl-phenyl)-propionamide (92 mg, 32%) as a white solid: [α]28589=−8.9° (c=0.1, methanol); ES-HRMS m/e calcd for C22H31N3O4S (M+H)+ 434.2108, observed 434.2108; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.03 (s, 3H, CH3), 1.05 (s, 3H, CH3), 1.12 (m, 2H, CH2), 1.37-1.79 (m, 8H, 4×CH2), 2.13 m, 1H, CH), 3.21 (s, 3H, SO2CH3), 3.86 (s, 2H, NCH2), 3.93 (m, 1H, ArCHCO), 4.64 (s, 1H, OH), 6.46 (d, J=2.2 Hz, 1H, Ar), 7.50 (d, J=2.2 Hz, 1H, Ar), 7.61 (t, J=7.7 Hz, 1H, Ar), 7.73 (d, J=7.7 Hz, 1H, Ar), 7.82 (d, J=7.7 Hz, 1H, Ar), 7.93 (s, 1H, Ar), 10.78 (s, 1H, NH).
