Potassium Carbonate → 3-Fluoro-5-(5-((2-methylthiazol-4-yl)ethynyl)pyridin-2-yl)benzonitrile

温度

80 °C

2-chloro-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (30 mmol, 7.02 g) and 3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (30 mmol, crude material, above procedure), dichlorobis(triphenylphosphine)palladium(II) (1.5 mmol, 1.05 g), and potassium carbonate (120 mmol, 16.6 g) were added to deoxygenated DME:water (1:1, 300 mL) at room temperature. The reaction was warmed to 80° C. and stirred overnight under nitrogen, then partitioned in a separatory funnel with EtOAc (500 mL) and water (300 mL). The organic layer was washed with one additional portion of water (100 mL) and the combined aqueous layers back extracted with EtOAc (100 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The crude residue was chromatographed on SiO2, eluting with 30% EtOAc in hexanes, to afford the title compound as a tan solid. 1H-NMR (CDCl3, 500 MHz) δ 8.89 (m, 1H), 8.17 (dd, 1H), 8.04 (m, 1H), 7.98 (dd, 1H), 7.75 (d, 1H), 7.50 (s, 1H), 7.42 (m, 1H), 2.79 (s, 3H). MS (ESI) 320.0 (M+H+).

1. customto deoxygenated DME:water (1:1, 300 mL) at room temperature
2. custompartitioned in a separatory funnel with EtOAc (500 mL) and water (300 mL)
3. washThe organic layer was washed with one additional portion of water (100 mL)
4. extractionthe combined aqueous layers back extracted with EtOAc (100 mL)
5. dry with materialThe combined organic layers were dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe crude residue was chromatographed on SiO2
9. washeluting with 30% EtOAc in hexanes

ORDレコード

ord-4944e104623b42d594e55d2f5eb065ce

出典データセット

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08609852B2