反应详情

温度

80 °C

Title compound was prepared following the carbonylative triazole synthesis procedure (referred herein as Procedure I as described in: Staben, S. T.; Blaquiere, N Angew. Chem. Int. Ed. 2010, 49, p. 325. To a solution of 10-bromo-9-fluoro-3-iodo-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide (300 mg, 0.66 mmol) and acetamidine hydrochloride (1.50 equiv., 99.1 mg, 0.99 mmol) in DMF (3.3 mL, 0.2M) was added triethylamine (0.66 mL, 1.0 mL/mmol). The solution was purged with nitrogen gas. Palladium (II) acetate (0.05 equiv., 7.4 mg) and xantphos (0.05 equiv., 19.8 mg) were added and the flask was purged with a carbon monoxide balloon. The reaction was heated to 80° C. for 2 hours. The CO balloon was removed and the reaction mixture was cooled to room temperature. 2,2,2-trifluoroethylhydrazine (70% in H2O, 3.0 equiv., 0.25 mL) and acetic acid (2.6 mL, 4 mL/mmol) were added and the mixture was heated to 80° C. for 1 hour. The reaction was cooled to room temperature, diluted with methylene chloride and filtered over celite. 1N NaOH was added and the solution was extracted with methylene chloride 3×. The organic layers were combined, dried with Na2SO4 and concentrated. The crude residue was purified by flash column chromatography (10-100% ethyl acetate in hexanes) to give a yellow solid (282 mg).

1. customThe solution was purged with nitrogen gas
2. customthe flask was purged with a carbon monoxide balloon
3. customThe CO balloon was removed
4. temperaturethe reaction mixture was cooled to room temperature
5. temperaturethe mixture was heated to 80° C. for 1 hour
6. temperatureThe reaction was cooled to room temperature
7. filtrationfiltered over celite
8. addition1N NaOH was added
9. extractionthe solution was extracted with methylene chloride 3×
10. dry with materialdried with Na2SO4
11. concentrationconcentrated
12. customThe crude residue was purified by flash column chromatography (10-100% ethyl acetate in hexanes)