反应详情

A mixture of example 121 (125 mg, 0.308 mmol), tert-butyl 4-(methylsulfonyloxy)piperidine-1-carboxylate (129 mg, 0.462 mmol) and cesium carbonate (301 mg, 0.924 mmol) was heated at 90° C. for 24 hr. LCMS indicated ˜90% completion of the reaction. Two products were observed. The mixture was dropped into brine and the resulting precipitate was collected by filtration and rinsed with water. The partially dried solids were taken up in EtOAc, dried over magnesium sulfate and concentrated. The residue was purified with a Biotage silica gel cartridge eluting with 50-100% EtOAc/Heptane to give tert-butyl 4-[(6′-amino-5′-{(1R)-1-[5-fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl]ethoxy}-3,3′-bipyridin-6-yl)oxy]piperidine-1-carboxylate (117 mg).

1. custom˜90% completion of the reaction
2. filtrationthe resulting precipitate was collected by filtration
3. washrinsed with water
4. dry with materialdried over magnesium sulfate
5. concentrationconcentrated
6. customThe residue was purified with a Biotage silica gel cartridge
7. washeluting with 50-100% EtOAc/Heptane