Reaction Steps
To a solution of (S)-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid (0.086 g, 0.28 mmol) in dry N,N-dimethylformamide (5 mL) was added 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 0.068 g, 0.34 mmol), and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.183 g, 0.41 mmol). To this mixture was added N,N-diisopropylethylamine (0.109 g, 0.85 mmol) and the resulting mixture stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with an ammonium chloride solution, a saturated sodium bicarbonate solution, saturated sodium chloride solution and then dried over magnesium sulfate. The solvents were evaporated and the residue was purified by AnaLogix flash chromatography (Teledyne Isco RediSep Flash Column 12 g, 100% ethyl acetate) which afforded (S)-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (0.102 g, 75%) as a light yellow solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 0.91 (t, J=7.2 Hz, 3H), 1.10-1.43 (m, 2H), 1.25 (s, 3H), 1.30 (s, 3H), 1.77 (q, J=7.7 Hz, 2H), 3.73 (dd, J=8.5, 6.0 Hz, 1H), 4.00 (dd, J=8.5, 6.3 Hz, 1H), 4.04-4.20 (m, 2H), 4.24-4.41 (m, 2H), 4.61 (d, J=18.7 Hz, 1H), 4.79 (t, J=7.7 Hz, 1H), 5.03 (s, 1H), 6.44 (d, J=2.1 Hz, 1H), 7.27-7.51 (m, 3H), 7.60 (d, J=2.1 Hz, 1H), 10.75 (s, 1H).
