Water → 8-[3-((R)-5-Amino-3-difluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenylamino]-[1,7]naphthyridine-3-carbonitrile

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Reaction Steps

[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.

Provenance & Evidence