Reaction #47379
ord-d1e9fb0213874a18a1adb61a1ef5447b
Reaction equation
Reactants
Reagents
Solvents
Conditions
Workup
- 1workup.ADDITIONwas added
- 2WashThe mixture was washed with saturated aqueous ammonium chloride solution (1 mL)
- 3Otherevaporated
- 4Otherthe 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
Procedure
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, 93 mg, 0.29 mmol) in dichloromethane (1.00 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (60 mg, 0.31 mmol) and 1-hydroxybenzotriazole (40 mg, 0.30 mmol). The resulting solution was stirred for 5 min before N3,N3-dimethyl-[1,2,4]thiadiazole-3,5-diamine (prepared in German Patent DE959191 Example 8, 50 mg, 0.35 mmol) was added and the resulting mixture stirred at 25° C. overnight. The mixture was washed with saturated aqueous ammonium chloride solution (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-dimethylamino-[1,2,4]thiadiazol-5-yl)-amide (47 mg, 36%) as a yellow solid: HR-ES-MS m/z calculated for C20H24ClN5O3S [M+H]+ 450.1361, observed 450.1360; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.89 (d, J=6.4 Hz, 3H), 0.93 (d, J=6.4 Hz, 3H), 1.44 (br. s., 1H), 1.51-1.72 (m, 1H), 1.72-1.98 (m, 1H), 3.02 (s, 6H), 4.25 (d, J=18.4 Hz, 1H), 4.50 (d, J=18.4 Hz, 1H), 4.81 (s, 1H), 4.97 (dd, J=10.9, 4.5 Hz, 1H), 7.36 (td, J=7.8, 1.5 Hz, 1H), 7.45 (td, J=7.8, 1.4 Hz, 1H), 7.52 (dd, J=7.8, 1.5 Hz, 1H), 7.64 (dd, J=7.8, 1.4 Hz, 1H), 13.08 (s, 1H).