反应详情

温度

115 °C

Under a nitrogen atmosphere, the (S)-tert-butyl 3-(4-chloro-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrrolo[3,2-c]pyridin-1-yl)pyrrolidine-1-carboxylate (120 mg) obtained in Step 3,2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (BINAP) (26 mg), sodium tert-butoxide (72 mg), benzophenone imine (92 mg), and tris(dibenzylideneacetone)dipalladium (36 mg) were suspended in toluene (10 ml), and the result was stirred at 115° C. for 90 minutes. After dilution with ethyl acetate, celite filtration was performed. The solvent was distilled off under reduced pressure. Hydroxyaminehydrochloride (366 mg), sodium bicarbonate (442 mg), methanol (16 ml), and water (4 ml) were added to the resulting residue, and the resulting mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure. Thereafter, ethyl acetate and a saturated sodium chloride solution were added to separate the organic layer. The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by basic silica gel column chromatography (developing solvent: hexane/ethyl acetate) to obtain the title compound as a colorless, amorphous substance (35 mg). Physical properties: m/z [M+H]+ 463.4

1. filtrationAfter dilution with ethyl acetate, celite filtration
2. distillationThe solvent was distilled off under reduced pressure
3. additionHydroxyaminehydrochloride (366 mg), sodium bicarbonate (442 mg), methanol (16 ml), and water (4 ml) were added to the resulting residue
4. stirringthe resulting mixture was stirred at room temperature for 2 hours
5. distillationThe solvent was distilled off under reduced pressure
6. additionThereafter, ethyl acetate and a saturated sodium chloride solution were added
7. customto separate the organic layer
8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
9. distillationthe solvent was distilled off under reduced pressure
10. customThe resulting residue was purified by basic silica gel column chromatography (developing solvent: hexane/ethyl acetate)