1-Hydroxybenzotriazole → HCID 44252461, compound

Participants

Reaction Conditions

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, 94 mg, 0.29 mmol) in dichloromethane (1.00 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (61 mg, 0.32 mmol) and 1-hydroxybenzotriazole (42 mg, 0.31 mmol). The resulting solution was stirred for 5 min before 3-methoxymethyl-[1,2,4]thiadiazol-5-ylamine (50 mg, 0.34 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-methoxymethyl-[1,2,4]thiadiazol-5-yl)-amide (62 mg, 47%) as a light yellow solid: HR-ES-MS m/z calculated for C20H23ClN4O4S [M+H]+ 451.1202, observed 451.1202; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.92 (d, J=6.6 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H), 1.48 (br. s., 1H), 1.60-1.76 (m, 1H), 1.79-1.95 (m, 1H), 3.33 (s, 3H), 4.30 (d, J=18.1 Hz, 1H), 4.51 (d, J=18.1 Hz, 1H), 4.52 (s, 2H), 4.84 (s, 1H), 5.02 (dd, J=10.9, 4.5 Hz, 1H), 7.37 (td, J=7.5, 0.9 Hz, 1H), 7.47 (t, J=7.5 Hz, 1H), 7.54 (d, J=7.5 Hz, 1H), 7.66 (d, J=7.5 Hz, 1H), 13.40 (s, 1H).

Provenance & Evidence