Cesium carbonate → 1-(4'-{3-Methyl-4-[6-bromo-pyridin-2-ylamino]-isoxazol-5-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid ethyl ester

Temperature

70 °C

1-[4′-(4-Amino-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester (2.7 g, 6.7 mmol), 2,6-dibromopyridine (2.3 g, 10.0 mmol), cesium carbonate (3.04 g, 9.4 mmol), and BINAP (0.187 g, 0.3 mmol) were stirred in THF (100 mL) at room temperature and bubbled with nitrogen for 1 hr. Palladium(II) acetate (0.068 g, 0.20 mmol) was added, and the mixture was warmed to 70° C., stirred for 72 hrs, then cooled to room temperature. The resulting mixture was diluted with EtOAc (300 mL) and extracted with H2O (2×100 mL). The organic layer was dried over MgSO4, filtered and concentrated, and the crude residue was purified on silica gel (0% to 80% EtOAc in hexane gradient) to afford the title compound.

1. custombubbled with nitrogen for 1 hr
2. temperaturecooled to room temperature
3. extractionextracted with H2O (2×100 mL)
4. dry with materialThe organic layer was dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. customthe crude residue was purified on silica gel (0% to 80% EtOAc in hexane gradient)

ORD record

ord-a5a687941e0640b99c39db11a5192584

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08541587B2