Triethylamine → 3-(4-(2-(2-(1H-Imidazol-4-yl)phenoxy)ethyl)phenyl)-1-hydroxy-1-(tetrahydro-2H-pyran-4-yl)urea

Participants

Reaction Steps

A mixture of 4-(2-(2-(1-trityl-1H-imidazol-4-yl)phenoxy)ethyl)aniline (113 mg, 0.217 mmol), triphosgene (21 mg, 0.07 mmol) and triethylamine (0.04 mL, 0.260 mmol) in dry dichloromethane (6 mL) was heated at reflux for 2 h and then cooled with an ice bath. To this mixture was added N-(tetrahydro-2H-pyran-4-yl)hydroxylamine (76 mg, 0.650 mmol). The reaction mixture was stirred at room temperature for 2 h. The solvent was removed and the crude was dissolved in methanol (4 mL) and acetic acid (1 mL). The reaction mixture was heated at 80° C. for 2 h. The reaction mixture was basified with aqueous 10% NaOH and the aqueous layer extracted with ethyl acetate (2×30 mL). The combined organic extracts were washed with brine (15 mL), dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography using 5% MeOH/dichloromethane as an eluent at afford the desired product as a yellowish solid (30 mg, 33%). 1H NMR: 1.63 (d, 2H, J=10.4 Hz), 1.98-2.07 (m, 2H), 3.15 (t, 3H, J=5.6 Hz), 3.46 (t, 2H, J=11.6 Hz), 3.78 (s, 1H), 4.02 (dd, 2H, J=11.2 Hz, 4 Hz), 4.36-4.45 (m, 4H), 6.98-7.03 (m, 3H), 7.19-7.27 (m, 3H), 7.30-7.42 (m, 3H), 7.66 (s, 1H), 8.14 (s, 1H).

Provenance & Evidence