反应详情

The product of Step 1 (5.12 g, 18.7 mmol), cis-2,6-dimethyl piperazine (3.20 g, 28.1 mmol), sodium tert-butoxide (5.39 g, 56.1 mmol), tris(dibenzylideneacetone)dipalladium(0) (343 mg, 0.37 mmol) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (444 mg, 1.12 mmol) were heated at reflux for 16 hours in 1,4-dioxane (50 ml). The solution was filtered through celite washing through with ethyl acetate. The filtrate was concentrated in vacuo, and the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic phase was washed with water, 50% saturated brine solution, brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by chromatography on silica gel (ethyl acetate, then a gradient of dichloromethane to 10% 2M methanolic ammonia in dichloromethane) to afford the title compound. MS (ES+) m/e 266 [M+H]+.

1. filtrationThe solution was filtered through celite
2. washwashing through with ethyl acetate
3. concentrationThe filtrate was concentrated in vacuo
4. customthe residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
5. washThe organic phase was washed with water, 50% saturated brine solution, brine
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated in vacuo
8. customThe residue was purified by chromatography on silica gel (ethyl acetate