反应详情

温度

75 °C

(4-ethoxy-3-fluorophenyl)boronic acid (0.072 g, 0.39 mmol), cesium carbonate (0.096 g, 0.3 mmol) and 1,1′-bis(diphenylphosphino)ferrocenepalladium (0.008 g, 0.010 mmol) complex with dichloromethane, were subsequently added to a degassed solution of 4-({(4S)-6-iodo-1-oxo-7-[3-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl}methyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (0.06 g, 0.1 mmol) in 3 ml of 1,4-dioxane and 1 ml of water, under argon. The mixture was heated at 100° for 3 hours in a sealed vial. The reaction was portioned between ethyl acetate and water, the organic layer dried over sodium sulphate and the solvent removed in vacuo. 4-({(4S)-6-(4-ethoxy-3-fluorophenyl)-1-oxo-7-[3-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl}methyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide was submitted to the next step without purification. The crude was dissolved in a mixture 1:1 of water (2 ml) and 4N HCl in dioxane (2 ml) and heated at 75° C. until deprotection was completed. After evaporation under vacuo, purification by RP-HPLC afforded the title compound as a white solid.

1. temperatureThe mixture was heated at 100° for 3 hours in a sealed vial
2. dry with materialthe organic layer dried over sodium sulphate
3. customthe solvent removed in vacuo
4. custom4-({(4S)-6-(4-ethoxy-3-fluorophenyl)-1-oxo-7-[3-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl}methyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide was submitted to the next step without purification
5. dissolutionThe crude was dissolved in a mixture 1:1 of water (2 ml) and 4N HCl in dioxane (2 ml)
6. customAfter evaporation
7. customunder vacuo, purification by RP-HPLC