反应详情

温度

85 °C

A mixture of potassium (4-((4-chlorophenyl)(hydroxy)methyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)thiophen-2-yl)trifluoroborate (0.133 g, 0.276 mmol), 4-bromo-pyridine-2-carbonitrile (60.6 mg, 0.331 mmol), 2-dicyclohexylphosphino-2′,6′-di-1-propoxy-1,1′-biphenyl (24.8 mg, 0.0533 mmol), palladium acetate (4.6 mg, 0.020 mmol) and sodium carbonate (77 mg, 0.73 mmol) in ethanol (6.2 mL, 110 mmol) was degassed with argon and then heated at 85° C. for 13 h. The mixture was absorbed on silica gel and purified by chromatography to afford an intermediate. LCMS: (AA) ES+ 478.1, 480.0. This intermediate in 1,4-dioxane (2.0 mL, 26 mmol), tert-butyl alcohol (2.0 mL, 21 mmol) and 4.00 M HCl in dioxane (3.0 mL, 14 mmol) was heated at 60° C. for 1 h. The mixture was evaporated to dryness and then purified by HPLC to afford 4-(4-((4-chlorophenyl)(hydroxy)methyl)-5-(4H-1,2,4-triazol-3-yl)thiophen-2-yl)picolinonitrile (12.4 mg, 11.4%). LCMS: (FA) ES+ 394.3, 396.1. 1H NMR (400 MHz, d6-DMSO) δ: 14.69-13.48 (br, 1H), 8.69 (d, J=6.79 Hz, 2H), 8.45 (s, 1H), 8.08-7.88 (m, 2H), 7.56 (d, J=8.39 Hz, 2H), 7.35 (d, J=8.40 Hz, 2H), 6.79 (s, 1H).

1. customwas degassed with argon
2. customThe mixture was absorbed on silica gel
3. custompurified by chromatography
4. customto afford an intermediate
5. customThe mixture was evaporated to dryness
6. custompurified by HPLC