反应详情

温度

50 °C

HCl in dioxane (0.654 ml, 2.61 mmol) was added to a suspension of (R)-6-(3-((tert-butyldimethylsilyl)oxy)-2-hydroxypropyl)-5-(3-chlorophenyl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (250 mg, 0.523 mmol), 4-chlorothiazole-2-carbaldehyde (Intermediate H) (85 mg, 0.575 mmol) and bismuth triflate (103 mg, 0.157 mmol) in anhydrous ethanol (4 ml) and the mixture heated at 50° C. for 36 hours. Further portions of HCl in dioxane (0.654 ml, 2.61 mmol) were added as necessary to allow the reaction to run to completion. The mixture was cooled to room temperature and diluted with EtOAc (50 ml) and water (20 ml). The phases were separated and the aqueous phase extracted with EtOAc (3×30 ml). The combined organic extracts were washed with saturated NaHCO3(aq) (20 ml), water (20 ml) and brine (20 ml), dried over sodium sulfate and evaporated under vacuum. Purification by chromatography on silica, eluting with 10-70% EtOAc/hexane afforded the title compound as a mixture of diastereomers.

1. customthe reaction
2. temperatureThe mixture was cooled to room temperature
3. customThe phases were separated
4. extractionthe aqueous phase extracted with EtOAc (3×30 ml)
5. washThe combined organic extracts were washed with saturated NaHCO3(aq) (20 ml), water (20 ml) and brine (20 ml)
6. dry with materialdried over sodium sulfate
7. customevaporated under vacuum
8. customPurification by chromatography on silica
9. washeluting with 10-70% EtOAc/hexane