Реакция #485
ord-bea3ac5058c048368377611c2ed94139
Уравнение реакции
Растворители
Условия реакции
Методика
6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (558 mg, 2.73 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (750 mg, 2.73 mmol), Sodium tert-butoxide (394 mg, 4.09 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (119 mg, 0.19 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (175 mg, 0.19 mmol) were added to a microwave vial followed by toluene (11 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 10:90 as gradient. fr1 :160 mg approx 60% pure fr2: 804 mg purity 90-99% depending on wavelength, pH and solvent. Preparative purification with Gilson prep was performed on the combined mixture. 30-70% gradient was used. The first batch (38% of the crude) was lost due to the fact that the product gave **negative UV-signal** therefore didn't trigger any collection! The rest of the material was collected manually. The fractions were pooled together, concentrated in vacuo then tretaed 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 was dried overnight in a vacuum owen at 50°C.