反应详情

DIPEA (153.5 mg, 1.2 mmol) followed by HOBt (44.1 mg, 0.32 mmol) and EDCI (113.8 mg, 0.59 mmol) were added to a stirred solution of [(5-phenyl-isoxazole-3-carbonyl)-amino]-acetic acid (73.4 mg, 0.29 mmol) in DMF (2 mL). After 2 minutes of stirring, 3-(2,5-difluoro-phenoxy)-pyrrolidine hydrochloride (prepared by the method used for the synthesis of Intermediate 15) (70 mg, 0.29 mmol) was added and the resulting mixture was stirred at ambient temperature overnight. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was dried over sodium sulfate, concentrated under reduced pressure. Purification by column chromatography (using silica gel 60-120 and 50% EtOAc in hexane) afforded 45 mg (35.4% Yield) of 5-phenyl-isoxazole-3-carboxylic acid {2-[3-(2,5-difluoro-phenoxy)-pyrrolidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 428, 91.77%. 1H NMR (300 MHz, DMSO-d6): δ 8.8-8.68 (m, 1H), 8.0-7.9 (m, 2H), 7.6-7.5 (m, 3H), 7.4 (s, 1H), 7.34-7.2 (m, 2H), 6.9-6.75 (m, 1H), 5.3-5.0 (m, 2H), 4.2-4.0 (m, 2H), 3.9 (m, 1H), 3.8-3.7 (m, 1H), 3.7-3.5 (m, 2H), 2.3-2.2 (m, 1H), 2.1 (m, 1H).

1. additionwas added
2. stirringthe resulting mixture was stirred at ambient temperature overnight
3. customThe reaction mixture was partitioned between ethyl acetate and water
4. dry with materialThe organic layer was dried over sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customPurification by column chromatography (using silica gel 60-120 and 50% EtOAc in hexane)