反应详情

To a mixture of (3R)-1-(2-chloropyrimidin-4-yl)-3-ethyl-2-oxopyrrolidine-3-carbonitrile (100 mg) obtained in Step A of Example 8, 2-methyl-1,3-thiazol-5-amine (56 mg), potassium carbonate (110 mg) and dicyclohexyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (58 mg) in tert-butanol (1.0 mL) was added tris(dibenzylideneacetone)dipalladium(0) (22 mg), and the mixture was stirred for 5 hr with heated under reflux. The insoluble substance was removed by filtration through Celite, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate). To a solution of the obtained compound (26 mg) in ethanol (2.0 mL) was added 1 M hydrochloric acid (80 μL), and the mixture was stirred at room temperature for 5 min. The solvent was evaporated under reduced pressure, and the residue was recrystallized (ethanol) to give the title compound (15 mg).

1. temperaturewith heated
2. temperatureunder reflux
3. customThe insoluble substance was removed by filtration through Celite
4. customthe solvent was evaporated under reduced pressure
5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
6. additionTo a solution of the obtained compound (26 mg) in ethanol (2.0 mL) was added 1 M hydrochloric acid (80 μL)
7. stirringthe mixture was stirred at room temperature for 5 min
8. customThe solvent was evaporated under reduced pressure
9. customthe residue was recrystallized (ethanol)