Reaction Steps
A solution of (R)-3-cyclopentyl-2-(4-methanesulfonyl-3-methoxy-phenyl)-propionic acid (60 mg, 0.18 mmol) was dissolved in methylene chloride (5 mL) and N,N-dimethylformamide (one drop) and cooled to 0° C. To this solution was added dropwise a solution of oxalyl chloride in methylene chloride (2 M solution, 110 μL, 0.21 mmol) which produced gas evolution and it was then warmed to 25° C. and stirred for 1 h. After this time, the reaction was concentrated in vacuo to about 2 mL. In a separate round bottom flask was placed 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared as in Example 80, 31 mg, 0.20 mmol), 2,6-lutidine (32 μL, 0.28 mmol) and methylene chloride (5 mL) which was then cooled to 0° C. in an ice bath. To this solution was then added dropwise the above solution acid chloride. The reaction was then allowed to warm up to 25° C. and stirred for 16 h. After this time the reaction mixture was diluted with methylene chloride (5 mL) transferred to a separatory funnel and washed with a saturated aqueous sodium bicarbonate solution (10 mL) and then a 1 N aqueous hydrochloric acid solution (10 mL) and then dried over magnesium sulfate, filtered and concentrated in vacuo. Purification on an AnaLogix Intelliflash system (4 g column, 70% ethyl acetate/hexanes to 85% ethyl acetate/hexanes) afforded (R)-3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(4-methanesulfonyl-3-methoxy-phenyl)-propionamide (61 mg, 73%) as a white foam: [α]28589=−26.0° (c=0.10, methanol); ES-HRMS m/e calcd for C23H33N3O5S (M+H)+ 464.2214, observed 464.2211; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.03 (s, 3H, CH3), 1.04 (s, 3H, CH3), 1.10 (m, 2H, CH2), 1.35-1.80 (m, 8H, 4×CH2), 2.11 (m, 1H, CH), 3.20 (s, 3H, SO2CH3), 3.86 (s, 2H, NCH2), 3.90 (br, 1H, ArCHCO), 3.95 (s, 3H, OCH3), 4.65 (s, 1H, OH), 6.46 (s, 1H, Ar), 7.15 (d, Jo=8.2 Hz, 1H, Ar), 7.27 (s, 1H, Ar), 7.50 (s, 1H, Ar), 7.74 (d, Jo=8.2 Hz, 1H, Ar), 10.73 (s, 1H, NH).
