Reaction #73880

Reaction equation

1-[4′-(4-Amino-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester

2,6-dibromopyridine

cesium carbonate

BINAP

→

title compound

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

Solvents

EtOAc

THF

Conditions

Workup

1. 1
   Otherbubbled with nitrogen for 1 hr
2. 2
   Temperaturecooled to room temperature
3. 3
   Extractionextracted with H2O (2×100 mL)
4. 4
   DryingThe organic layer was dried over MgSO4
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated
7. 7
   Otherthe crude residue was purified on silica gel (0% to 80% EtOAc in hexane gradient)

Procedure

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.

Source