Reaction Steps
To a solution of (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (prepared as in Example 64, 60 mg, 0.19 mmol) in dichloromethane (1.00 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (40 mg, 0.21 mmol) and 1-hydroxybenzotriazole (27 mg, 0.20 mmol). The resulting solution was stirred for 5 min before 3-(4-methoxy-benzyl)-[1,2,4]thiadiazol-5-ylamine (50 mg, 0.23 mmol) was added and the resulting mixture stirred at 25° C. overnight. The mixture was washed with saturated ammonium chloride (1 mL), evaporated and the crude product purified by HPLC (Gilson semi-prep; Supelcosil ABZ+Plus 12 μM 25 cm×21.2 mm column 20-95% acetonitrile/water) which afforded (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [3-(4-methoxy-benzyl)-[1,2,4]thiadiazol-5-yl]-amide (48 mg, 49%) as a light yellow solid: HR-ES-MS m/z calculated for C26H27ClN4O4S [M+H]+ 527.1515, observed 527.1514; 1H NMR MHz, DMSO-d6) δ ppm 0.88 (d, J=6.6 Hz, 3H), 0.91 (d, J=6.6 Hz, 3H), 1.22 (t, J=7.5 Hz, 3H), 1.44 (br. s., 1H), 1.54-1.71 (m, 1H), 1.71-1.90 (m, 1H), 2.76 (q, J=7.5 Hz, 2H), 4.25 (d, J=18.4 Hz, 1H), 4.48 (d, J=18.4 Hz, 1H), 4.79 (s, 1H), 4.97 (dd, J=10.9, 4.8 Hz, 1H), 7.33 (td, J=7.8, 1.5 Hz, 1H), 7.43 (td, J=7.8, 1.4 Hz, 1H), 7.50 (dd, J=7.8, 1.5 Hz, 1H), 7.62 (dd, J=7.8, 1.4 Hz, 1H), 13.24 (s, 1H).
