Reaction Steps
A reaction of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-oxetan-3-yl-propionic acid (0.18 g, 0.56 mmol), 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in Example 80, 0.1 g, 0.64 mmol), and triethyl amine (0.17 ml, 1.24 mmol) in methylene chloride (15 mL) was cooled to 0° C. To this solution was added benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (0.25 g, 0.56 mmol). The reaction was allowed to warm to 25° C. and stirred for 24 h. After this time, the reaction was concentrated in vacuo. Purification on an AnaLogix Intelliflash system (40 g column, 3% methanol/methylene chloride to 5% methanol/methylene chloride) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-3-oxetan-3-yl-propionamide (0.1 g, 40%) as a 1:1 enantiomeric reaction as a white gummy solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 1.02 (s, 3H, CH3), 1.04 (s, 3H, CH3), 2.01-2.15 (m, 1H, CH of CH2), 2.32-2.47 (m, 1H, CH of CH2), 2.75-2.91 (m, 1H, CH), 3.31 (s, 3H, SO2CH3), 3.69-3.79 (m, 1H, ArCHCO), 3.85 (s, 2H, NCH2), 4.16-4.30 (m, 2H, 2×OCH of 2×OCH2), 4.47-4.57 (m, 2H, 2×OCH of 2×OCH2), 4.65 (s, 1H, OH), 6.44 (d, J=2.4 Hz, 1H, Ar), 7.52 (d, J=2.4 Hz, 1H, Ar), 7.57 (dd, Jo=8.3 Hz, Jm=1.4 Hz, 1H, Ar), 7.70 (d, Jm=1.4 Hz, 1H, Ar), 8.00 (d, Jo=8.3 Hz, 1H, Ar), 10.77 (s, 1H, NH).
