Cesium fluoride → 4'-Hydroxy-3'-pyridazin-4-ylbiphenyl-3-carbonitrile

Temperatur

60 °C

A mixture of 4′-hydroxy-3′-iodobiphenyl-3-carbonitrile (Preparation 120, 715 mg, 2.23 mmol), 4-(tributylstannyl)pyridazine (904 mg, 2.45 mmol) and cesium fluoride (677 mg, 4.46 mmol) in N,N-dimethylformamide (5 mL) was degassed under nitrogen. Then tetrakistriphenylphosphinepalladium (0) (258 mg, 0.22 mmol) and copper (I) iodide (85 mg, 0.45 mmol) were added, the reaction mixture was further degassed and then heated at 60° C. for 4 hours. The cooled reaction mixture was quenched with 10% ammonia (0.88M) in water (10 mL), diluted with ethyl acetate (20 mL) and then the mixture was stirred for 20 minutes. The resulting mixture was further diluted with ethyl acetate (10 mL) and the layers were separated. The organic layer was dried over anhydrous MgSO4, filtered and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with 10% dichloromethane in ethyl acetate to give the title compound (355 mg, 55%).

1. customwas degassed under nitrogen
2. customthe reaction mixture was further degassed
3. customThe cooled reaction mixture
4. customwas quenched with 10% ammonia (0.88M) in water (10 mL)
5. additiondiluted with ethyl acetate (20 mL)
6. additionThe resulting mixture was further diluted with ethyl acetate (10 mL)
7. customthe layers were separated
8. dry with materialThe organic layer was dried over anhydrous MgSO4
9. filtrationfiltered
10. concentrationthe filtrate was concentrated in vacuo
11. customThe residue was purified by flash chromatography on silica gel eluting with 10% dichloromethane in ethyl acetate

ORD-Eintrag

ord-47badeadc1b24e4cb3e5ab2040ca939a

Quelldatensatz

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08772293B2