反应详情

温度

80 °C

A mixture of ((8R)-10-(5-chlorofuran-2-yl)-5-(3-fluorophenyl)-1,3-dimethyl-2,4-dioxo-2,3,4,7,8,10-hexahydro-1H-pyrimido[4′,5′:3,4]pyrrolo[2,1-c][1,4]oxazin-8-yl)methyl methanesulfonate (117 mg, 0.217 mmol), cesium carbonate (142 mg, 0.435 mmol) and imidazole (22.51 mg, 0.331 mmol) in acetonitrile (6 mL) was heated at 80° C. for 16 hours, then at 85° C. for 3.5 hours. Further portions of imidazole (22.51 mg, 0.331 mmol) and cesium carbonate (142 mg, 0.435 mmol) were added and the mixture heated for a further 2 hours. The mixture was cooled to room temperature, diluted with water (30 ml) and extracted with DCM (2×30 ml). The combined organic extracts were washed with brine (30 ml) passed through a hydrophobic frit and evaporated under vacuum. Purification by chromatography on silica, eluting with 0-100% EtOAc/hexane then with 0-10% MeOH/DCM, afforded the title compound as a mixture of diastereomers.

1. temperaturethe mixture heated for a further 2 hours
2. temperatureThe mixture was cooled to room temperature
3. extractionextracted with DCM (2×30 ml)
4. washThe combined organic extracts were washed with brine (30 ml)
5. customevaporated under vacuum
6. customPurification by chromatography on silica
7. washeluting with 0-100% EtOAc/hexane