反应详情

温度

90 °C

A mixture of 6-bromo-3-methylquinazolin-4(3H)-one (Intermediate 19A) (0.46 g, 1.92 mmol), tert-butyl hexahydropyrrolo[3,4-c]pyrrole-2(1H) carboxylate (0.49 g, 2.31 mmol), potassium phosphate, tribasic (1.33 g, 5.77 mmol), 2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1-biphenyl (26.9 mg, 0.06 mmol) and tris(dibenzyllideneacetone)dipalladium (0) (17.6 mg, 0.02 mmol) in dioxane (10 mL) was heated at 90° C. for 20 h. The mixture was diluted with water and the product extracted into dichloromethane. The organic layer was evaporated to dryness, re-dissolved in methanol and purified using a 5 g SCX column. The mixture was then further purified on silica (25 g SNAP column on SP4). Eluting with dichloromethane to 60/40 dichloromethane/(2M NH3 in methanol) to afford tert-butyl 5-(3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (270 mg, 0.73 mmol).

1. extractionthe product extracted into dichloromethane
2. customThe organic layer was evaporated to dryness
3. dissolutionre-dissolved in methanol
4. custompurified
5. customThe mixture was then further purified on silica (25 g SNAP column on SP4)
6. washEluting with dichloromethane to 60/40 dichloromethane/(2M NH3 in methanol)