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, 104 mg, 0.32 mmol) in dichloromethane (1.00 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (69 mg, 0.36 mmol) and 1-hydroxybenzotriazole (46 mg, 0.34 mmol). The resulting solution was stirred for 5 min before 3-ethyl-[1,2,4]thiadiazol-5-ylamine (50 mg, 0.39 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 gradient) which afforded (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (3-ethyl-[1,2,4]thiadiazol-5-yl)-amide (83 mg, 59%) as a light yellow solid: HR-ES-MS m/z calculated for C20H23ClN4O3S [M+H]+ 435.1252, observed 435.1252; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.88 (d, J=6.4 Hz, 3H), 0.91 (d, J=6.4 Hz, 3H), 1.45 (br. s., 1H), 1.53-1.72 (m, 1H), 1.83 (br. s., 1H), 3.69 (s, 3H), 4.04 (s, 2H), 4.26 (d, J=18.4 Hz, 1H), 4.48 (d, J=18.4 Hz, 1H), 4.80 (s, 1H), 4.96 (dd, J=11.2, 4.5 Hz, 1H), 6.84 (d, J=8.5 Hz, 2H), 7.17 (d, J=8.5 Hz, 2H), 7.35 (td, J=7.8, 1.5 Hz, 1H), 7.45 (t, J=7.8 Hz, 1H), 7.51 (d, J=7.8 Hz, 1H), 7.64 (d, J=7.8 Hz, 1H), 13.28 (s, 1H).
