反应详情

DIPEA (143 mg, 1.1 mmol) was added to a stirred solution of [(1-phenyl-1H-imidazole-4-carbonyl)-amino]-acetic acid (prepared from Intermediate 68 by means of Step 3 of the General Scheme) (68 g, 0.27 mmol) in DMF (2 mL) followed by HOBt (39 mg, 0.29 mmol) and EDCI (56 mg, 0.29 mmol). After 2 minutes of stirring, 3-(3-fluoro-5-trifluoromethyl-phenoxy)-azetidine hydrochloride (prepared by the method used for the synthesis of Intermediate 71) (75 mg, 0.27 mmol) was added and it was stirred overnight at ambient temperature. Partitioning with cold water and ethyl acetate and concentration of the organic layer after drying over sodium sulfate afforded a residue which was purified by preparative HPLC to give 40 mg (31.4% Yield) of 1-phenyl-1H-imidazole-4-carboxylic acid {2-[3-(3-fluoro-5-trifluoromethyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 463, 99.18%. 1H NMR (300 MHz, DMSO-d6): δ 8.44 (d, 1H), 8.34 (d, 1H), 8.2 (t, 1H), 7.8 (d, 2H), 7.56 (t, 2H), 7.44 (m, 1H), 7.34 (d, 1H), 7.12 (m, 2H), 5.25 (m, 1H), 4.7 (m, 1H), 4.4 (m, 1H), 4.3 (m, 1H), 3.9 (m, 3H).

1. additionwas added
2. stirringit was stirred overnight at ambient temperature
3. customPartitioning with cold water and ethyl acetate and concentration of the organic layer
4. dry with materialafter drying over sodium sulfate
5. customafforded a residue which
6. customwas purified by preparative HPLC