Reaction Steps
A solution of (S)-4-methyl-2-[2-oxo-4-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acid (59 mg, 0.17 mmol) in N,N-dimethylformamide (1 mL) at 25° C. was treated with N,N-diisopropylethylamine (0.08 mL, 0.51 mmol), a solution of 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 41 mg, 0.20 mmol) in N,N-dimethylformamide (0.9 mL) and (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (115 mg, 0.26 mmol). The reaction was stirred at 25° C. overnight. At this time, the reaction was diluted with ethyl acetate (25 mL) and was washed with a saturated aqueous ammonium chloride solution (1×25 mL), a saturated aqueous sodium bicarbonate solution (1×25 mL) and a saturated aqueous sodium chloride solution (1×25 mL), dried over magnesium sulfate, filtered, rinsed with ethyl acetate and concentrated in vacuo. Purification by Analogix flash chromatography (24 g, 50-100% ethyl acetate/hexanes) afforded (S)-4-methyl-2-[2-oxo-4-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (43 mg, 47%) as a light yellow solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 0.90 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H), 1.25 (s, 3H), 1.30 (s, 3H), 1.33-1.66 (m, 2H), 1.64-1.83 (m, 5H), 2.57 (br. s., 2H), 2.67-2.80 (m, 2H), 3.73 (dd, J=8.5, 5.7 Hz, 1H), 4.00 (dd, J=8.5, 6.5 Hz, 1H), 4.07-4.14 (m, 1H), 4.18 (d, J=18.4 Hz, 1H), 4.26-4.41 (m, 1H), 4.56 (d, J=18.4 Hz, 1H), 4.65 (s, 1H), 4.88 (dd, J=10.3, 4.8 Hz, 1H), 6.43 (d, J=2.1 Hz, 1H), 6.97-7.07 (m, 2H), 7.18 (t, J=8.2 Hz, 1H), 7.59 (d, J=2.1 Hz, 1H), 10.76 (s, 1H).
