反应详情

[3-((R)-5-Amino-3-difluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-(3-bromo-[1,7]naphthyridin-8-yl)-amine (150 mg, 0.32 mmol), Zn powder (0.842 mg, 0.013 mmol), Zn(CN)2 (22.7 mg, 0.193 mmol), Zn(OAc)2 (2.36 mg 0.013 mmol), 1,1′-Bis-(diphenylphosphino)-ferrocene (0.54 mg, 0.001 mmol) and Tris(dibenzylideneacetone)-dipalladium (0) (0.29 mg 0.0003 mmol) were dissolved in DMF (4 ml) and water (0.04 ml) and heated under inert conditions to 95° C. for 2 h and then allowed to cool to rt. The reaction was quenched with water (10 ml) and NH3 (25%, 1 ml) and extracted with EtOAc (25 ml). The aq phase was extracted another 3× with EtOAc. The combined organic layer was washed with NaHCO3 solution and brine, treated with MgSO4 and filtered. The filtrated was concentrated and purified by column chromatography (silica gel; hexane/0-15% EtOAc) to give the desired product as a yellow solid.

1. customThe reaction was quenched with water (10 ml) and NH3 (25%, 1 ml)
2. extractionextracted with EtOAc (25 ml)
3. extractionThe aq phase was extracted another 3× with EtOAc
4. washThe combined organic layer was washed with NaHCO3 solution and brine
5. additiontreated with MgSO4
6. filtrationfiltered
7. concentrationThe filtrated was concentrated
8. custompurified by column chromatography (silica gel; hexane/0-15% EtOAc)