反应详情

DIPEA (193.9 mg, 1.5 mmol) followed by HOBt (53 mg, 0.29 mmol) and EDCI (75 mg, 0.39 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (92 g, 0.37 mmol) in DMF (3 mL) 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 room temperature overnight. The reaction mixture was partitioned between cold water and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. Purification by preparative HPLC afforded 35 mg (22.5% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[3-(5-cyano-2-methyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 416, 92.49%. 1H NMR (300 MHz, DMSO-d6): δ 13.8 (s, 1H), 8.2 (t, 1H), 7.74 (t, 2H), 7.42 (m, 2H), 7.3 (m, 3H), 7.16 (s, 1H), 7.08 (s, 1H), 5.2 (m, 1H), 4.7 (m, 1H), 4.4 (m, 1H), 4.2 (m, 1H), 3.8 (m, 3H).

1. additionwas added
2. stirringthe resulting mixture was stirred at room temperature overnight
3. customThe reaction mixture was partitioned between cold water and ethyl acetate
4. dry with materialThe organic layer was dried over sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customPurification by preparative HPLC