Ethyl Acetate → 3-(1-Pyridin-2-yl-1H-pyrrol-3-yl)-benzonitrile

Temperatur

84 °C

2-(3-Bromo-1H-pyrrol-1-yl)pyridine (1.34 g, 2 mmol), 3-cyanophenylboronic acid (0.59 g, 4 mmol), Pd(PPh3)4 (116 mg, 0.1 mmol) and potassium carbonate (560 mg, 4 mmol) were dissolved in a mixture of DME (18 mL) and H2O (2 mL) and degassed for 15 min with Ar (g). The reaction mixture was then heated at 84° C. for 18 h. At this time, a further 0.25 eq. of 3-cyanophenylboronic acid (0.15 g, 1 mmol) was added and heating was continued. After a total of 42 h, the reaction mixture was cooled to rt, H2O (40 mL) and EtOAc (40 mL) were added and the reaction mixture shaken, the EtOAc layer was separated and the aqueous layer shaken with EtOAc (2×30 mL). The combined organic layers were dried over Na2SO4 and concentrated to a yellow oil. This was purified by liquid chromatography on silica gel eluting with EtOAc:hexane (3:7) to afford a white waxy solid that was further purified by liquid chromatography on silica gel eluting with dichloromethane to afford 3-(1-pyridin-2-yl-1H-pyrrol-3-yl)benzonitrile as a colorless oil. 1H NMR (CD3Cl, 300 MHz) δ 8.49-8.52 (1H, m), 7.66 (1H, ddd), 7.47-7.51 (2H, m), 7.33-7.39 (3H, m), 7.24 (1H, ddd), 6.91 (1H, d), 6.51-6.52 (1H, m), 6.43 (1H, dd). MS (ESI) 246 (M+H)+.

1. customdegassed for 15 min with Ar (g)
2. temperatureheating
3. temperatureAfter a total of 42 h, the reaction mixture was cooled to rt
4. customthe EtOAc layer was separated
5. stirringthe aqueous layer shaken with EtOAc (2×30 mL)
6. dry with materialThe combined organic layers were dried over Na2SO4
7. concentrationconcentrated to a yellow oil
8. customThis was purified by liquid chromatography on silica gel eluting with EtOAc:hexane (3:7)
9. customto afford a white waxy solid
10. customthat was further purified by liquid chromatography on silica gel eluting with dichloromethane

ORD-Eintrag

ord-69cc0e4ccf5649e68ff54e8cafc88081

Quelldatensatz

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07371767B2