反应详情

温度

100 °C

A Schlenck flask was charged with palladium acetate (0.0966 g, 0.430 mmol), triphenylphosphine (0.4513 g, 1.721 mmol), and 1,4-dioxane (6 mL) and the mixture was stirred for 5 min until it turned bright yellow. 8-Bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridine (0.500 g, 2.15 mmol), 2-methoxybenzeneboronic acid (0.490 g, 3.23 mmol), N,N-dimethylformamide (10.00 mL), and 1.00 N sodium carbonate in water (4.3 mL, 4.3 mmol) were added successively and the reaction was heated at 80° C. overnight, cooled to room temperature, diluted with dichloromethane, filtered through diatomaceous earth and concentrated. The reaction was purified via chromatography (silica gel 10%→20% ethyl acetate in hexanes) and concentrated to give 2-chloro-8-(2-methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridine (0.464 g, 83%). MS=260 (MH)+. 311b) To an oven-dried Schlenck flask under an atmosphere of argon was added 2-chloro-8-(2-methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridine (0.460 g, 1.77 mmol), 7-amino-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester (0.558 g, 2.12 mmol), palladium acetate (0.0875 g, 0.390 mmol), 2,2-bis-dicyclohexylphosphanyl-biphenyl (0.242 g, 0.443 mmol), cesium carbonate (1.44 g, 4.43 mmol), followed by 1,4-dioxane (12.00 mL) and was degassed under an atmosphere of argon for 5 min and heated at 100° C. overnight, cooled at room temperature, diluted with dichloromethane, filtered through diatomaceous earth and concentrated. The reaction was purified via chromatography (silica gel 20%-30% ethyl acetate/hexanes) and concentrated to give 7-[8-(2-methoxy-phenyl)[1,2,4]triazolo[1,5-a]pyridin-2-ylamino]-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester (0.744 g, 87%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.54 (s, 1H), 8.78 (d, 1H), 7.55 (m, 2H), 7.45 (m, 2H), 7.35 (s, 1H) 7.15 (m, 1H), 7.05 (m, 3H), 3.74 (s, 3H), 3.48 (m, 4H), 2.78 (m, 4H), 1.41 (s, 9H): MS=486 (MH)+.

1. customwas degassed under an atmosphere of argon for 5 min
2. temperaturecooled at room temperature
3. additiondiluted with dichloromethane
4. filtrationfiltered through diatomaceous earth
5. concentrationconcentrated
6. customThe reaction was purified via chromatography (silica gel 20%-30% ethyl acetate/hexanes)
7. concentrationconcentrated