反応 #476
ord-eeeb45fc43db405282b2d52841087c19
反応方程式
反応条件
実験手順
6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (528 mg, 2.58 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (710 mg, 2.58 mmol), Sodium tert-butoxide (373 mg, 3.88 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (113 mg, 0.18 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (166 mg, 0.18 mmol) were added to a microwave vial followed by toluene (10.5 mL). The reaction mixture was flushed with nitrogen and the mixture was heated to 100°C and stirred overnight. The reaction was complete. The solids were filtered off and washed with ethyl acetate. The organic solution was extracted by sat NaHCO3 solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography using DCM : [DCM:MeOH:NH3=90:10:1] = 100:0 to 60:40 as gradient. The product was obtained as yellow foam 766 mg purity 95-99% depending on wavelength (95% on 220nm). The compound was dissolved in DCM and treated with activated carbon, then filtered and concentrated. The purity was **not** increased by the treatment! Preparative purification with Gilson prep was performed, 30-70% gradient was used. The material was collected manually. The fractions were pooled together, concentrated in vacuo then treated with DCM and sat NaHCO3 solution. The phases were separated, the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The product was obtained as white foam and was dried overnight in a vacuum oven at 40°C.