Reaction Steps
(R)-2-(4-Methanesulfonyl-3-methyl-phenyl)-3-((R)-3-oxo-cyclopentyl)-propionic acid (prepared in Example 122, 65 mg, 0.20 mmol) was dissolved in methylene chloride (2 mL) and N,N-dimethylformamide (two drops) at 25° C. under argon. 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 stirred at 25° C. for 30 minutes after which time it was concentrated in vacuo. The residue was then dissolved in methylene chloride (2 mL) and added dropwise into a solution of 3-(3-amino-pyrazol-1-yl)-propan-1-ol (prepared in Example 23, 29 mg, 0.20 mmol), 2,6-lutidine (46 μL, 0.40 mmol) and methylene chloride (2 mL) at 0° C. It was then allowed to warm to 25° C. and stirred for 1 h. After this time, the reaction was quenched with a small amount of methanol and diluted with methylene chloride and then concentrated with silica gel (2 g) in vacuo and purified on Biotage Flash chromatography system (40S column, silica gel, 80% ethyl acetate/hexanes to 10% methanol/ethyl acetate) to afford (R)—N-[1-(3-hydroxy-propyl)-1H-pyrazol-3-yl]-2-(4-methanesulfonyl-3-methyl-phenyl)-3-((R)-3-oxo-cyclopentyl)-propionamide (74 mg, 83%) as a colorless gum: [α]32589=−23.3° (c=0.15, methanol); ES-HRMS m/e calcd for C22H29N3O5S (M+H)+ 448.1901, observed 448.1901; 1H NMR (300 MHz, DMSO-d6) δ 1.50 (m, 1H, CH), 1.76-2.29 (m, 10H, 5×CH2), 2.62 (s, 3H, ArCH3), 3.18 (s, 3H, SO2CH3), 3.33 (m, 2H, OCH2), 3.90 (m, 1H, ArCHCO), 4.01 (t, J=6.9 Hz, 2H, NCH2), 4.56 (t, J=5.1 Hz, 1H, OH), 6.41 (d, J=2.2 Hz, 1H, Ar), 7.45 (brs, 1H, Ar), 7.46 (brd, 1H, Ar), 7.54 (d, J=2.2 Hz, 1H, Ar), 7.85 (d, Jo=8.6 Hz, 1H, Ar), 10.78 (s, 1H, NH).
