反应详情

To a suspension of 4-aminopyridine (164 mg, 1.74 mmol) in 3.3 mL of dichloromethane under inert atmosphere was added a 2M solution of trimethyl aluminium in toluene (0.87 mL, 1.74 mmol) and the mixture was stirred during 20 minutes at room temperature. Next, this mixture was cooled in an ice-water bath and a solution of di-tert-butyl 9-((5-chloro-4-oxo-4H-pyrrolo[1,2-d][1,3,4]oxadiazin-2-yl)methyl)-9H-purin-6-ylimidodicarbonate (150 mg, 0.29 mmol) in 2.2 mL of dry dichloromethane was added stirring the mixture during 3 days at room temperature. At the end of this period, the reaction mixture was cooled-down with an ice-water bath and mL of water were added followed by a 5% aqueous solution disodium tartrate dihydrate. The resulting mixture was purified directly by reverse phase chromatography (C-18 silica from Waters, water/1:1 acetonitrile-methanol as eluents 0% to 100%). After purification were obtained 139 mg of tert-butyl 9-(2-(3-chloro-2-(pyridin-4-ylcarbamoyl)-1H-pyrrol-1-ylamino)-2-oxoethyl)-9H-purin-6-ylcarbamate (93% yield).

1. temperatureNext, this mixture was cooled in an ice-water bath
2. stirringstirring the mixture during 3 days at room temperature
3. temperatureAt the end of this period, the reaction mixture was cooled-down with an ice-water bath
4. customThe resulting mixture was purified directly by reverse phase chromatography (C-18 silica from Waters, water/1:1 acetonitrile-methanol as eluents 0% to 100%)
5. customAfter purification