Reaction Steps
(R)-3-cyclopentyl-2-[4-(propane-2-sulfonyl)-phenyl]-propionic acid (100 mg, 0.31 mmol) was dissolved in methylene chloride (3 mL) and N,N-dimethylformamide (three drops) at 25° C. under argon. To this solution was added dropwise a solution of oxalyl chloride in methylene chloride (2 M solution, 180 μL, 0.33 mmol) which produced gas evolution and it was then stirred at 25° C. for 15 minutes after which time it was concentrated in vacuo. The residue was then dissolved in methylene chloride (3 mL) and added dropwise into a solution of 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared as in Example 80, 50 mg, 0.31 mmol), 2,6-lutidine (100 μL, 0.62 mmol) and methylene chloride (3 mL) at 0° C. It was then allowed to warm to 25° C. and stirred for 3 h. After this time, the reaction was quenched with a small amount of methanol and diluted with methylene chloride. It was then washed with 1 N aqueous hydrochloric acid solution and saturated aqueous brine solution dried over sodium sulfate and then concentrated with silica gel (2 g) in vacuo and purified on Biotage Flash chromatography system (40S column, silica gel, 60% ethyl acetate/hexanes to 100% ethyl acetate) to afford (R)-3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(propane-2-sulfonyl)-phenyl]-propionamide (83 mg, 58%) as a white foam: [α]30589=−8.3° (c=0.18, methanol); ES-HRMS m/e calcd for C24H35N3O4S (M+H)+ 462.2421, observed 462.2421; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.03 (s, 3H, CH3), 1.04 (s, 3 H, CH3), 1.11 (m, 2H, CH2), 1.13 (d, J=6.9 Hz, 6H, 2×CH3), 1.35-1.80 (m, 8H, 4×CH2), 2.10 (m, 1H, CH), 3.36 (m, 1H, SO2CH), 3.86 (s, 2H, NCH2), 3.93 (m, 1H, ArCHCO), 4.65 (s, 1H, OH), 6.46 (d, J=2.4 Hz, 1H, Ar), 7.50 (d, J=2.4 Hz, 1H, Ar), 7.64 (d, J=8.4 Hz, 2H, Ar), 7.80 (d, J=8.4 Hz, 2H, Ar), 10.79 (s, 1H, NH).
