Reaction Steps
A solution of (S)-2-[4-(benzooxazol-4-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid methyl ester (prepared as in Example 241, 0.137 g, 0.40 mmol) in tetrahydrofuran (10 mL) and water (10 mL) was treated with lithium hydroxide monohydrate (0.033 g 0.77 mmol) and the resulting mixture stirred at room temperature for 1.25 h. The mixture was concentrated in vacuo and the residue treated with acetonitrile, and concentrated in vacuo (repeated 2 additional times). The residue was treated with N,N-dimethylformamide and to this mixture was added 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 0.156 g, 1.00 mmol), N,N-diisopropylethylamine (0.180 g, 1.39 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.616 g, 1.39 mmol) at 0° C. The mixture was warmed to room temperature and stirred for 18 h. The mixture was concentrated in vacuo and the residue dissolved in ethyl acetate, washed with aqueous saturated ammonium chloride, brine, and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated in vacuo. The residue was purified by reverse phase HPLC (C18, 20×150 mm column, 30% to 100% acetonitrile/water) to afford (S)-2-[4-(benzooxazol-4-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide (0.055 g, 31%) as a tan solid: HR-ES-MS m/z calculated for C24H29N5O5 [M+H]+ 468.2242, observed 468.224; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.91 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H), 1.05 (br. s., 3H), 1.06 (br. s., 3H), 1.36-1.64 (m, 2H), 1.68-1.86 (m, 1H), 3.89 (s, 2H), 4.25 (d, J=18.4 Hz, 1H), 4.65 (d, J=18.4 Hz, 1H), 4.68 (s, 1H), 4.86-4.95 (m, 1H), 4.88 (s, 1H), 6.45 (d, J=2.1 Hz, 1H), 7.38 (d, J=8.0 Hz, 1H), 7.53 (t, J=8.0 Hz, 1H), 7.54 (d, J=2.1 Hz, 1H), 7.76 (d, J=8.0 Hz, 1H), 8.81 (s, 1H), 10.80 (s, 1H).
