反应详情

DIPEA (193.9 mg, 1.5 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) (92 mg, 0.37 mmol) in DMF (3 mL) followed by HOBt (53.2 mg, 0.39 mmol) and EDCI (75.5 mg, 0.39 mmol). After 2 minutes of stirring, 3-(azetidin-3-yloxy)-4-methyl-benzonitrile hydrochloride (prepared by the method used for the synthesis of Intermediate 71) (84 mg, 0.37 mmol) was added and the resulting mixture was stirred at ambient temperature overnight. 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 afford 29 mg (18.7% Yield) of 1-phenyl-1H-imidazole-4-carboxylic acid {2-[3-(5-cyano-2-methyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 416, 98.6%. 1H NMR (300 MHz, DMSO-d6): δ 8.38 (d, 1H), 8.28 (d, 1H), 8.12 (t, 1H), 7.7 (d, 2H), 7.5 (t, 2H), 7.38 (m, 3H), 7.16 (s, 1H), 5.2 (m, 1H), 4.7 (t, 1H), 4.4 (m, 1H), 4.2 (m, 1H), 3.8 (m, 3H).

1. additionwas added
2. stirringthe resulting mixture was stirred at ambient temperature overnight
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