反应详情

温度

200 °C

A mixture of (4-chlorophenyl){5-(2-fluoropyridin-4-yl)-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-3-thienyl}methanol (80.0 mg, 0.170 mmol), ethanolamine (0.104 g, 1.70 mmol) and N,N-diisopropylethylamine (0.118 mL, 0.679 mmol) in dimethylsulfoxide (0.5 mL, 7 mmol) was heated at 200° C. for 1 h under argon. The reaction mixture was cooled, diluted with water and extracted with butanol. The butanol layer was collected and evaporated to a residue which was purified by chromatography (SiO2, elution with 0-20% MeOH in DCM) to afford the intermediate. The intermediate in 1,4-dioxane (1.0 mL, 13 mmol) and conc HCl (1.0 mL, 12 mmol) was stirred at rt for 1 h. The solvent was evaporated and the residue was purified by chromatography (SiO2, elution with 0-70% (MeOH/DCM/NH4OH, 13/85/2) in DCM) to afford 2-({4-[4-[(4-chlorophenyl)(hydroxy)methyl]-5-(4H-1,2,4-triazol-3-yl)-2-thienyl]pyridin-2-yl}amino)ethanol (17.6 mg, 24.2%). LCMS: (AA) ES+ 428.2, 430.0; 1H NMR (400 MHz, d6-DMSO) δ: 14.66-14.13 (m, 1H), 8.68 (s, 1H), 7.94 (d, J=5.30 Hz, 1H), 7.58-7.48 (m, 3H), 7.38-7.30 (m, 2H), 6.81-6.68 (m, 3H), 6.60 (s, 1H), 4.72 (s, 1H), 3.57-3.45 (m, 2H), 3.34 (d, J=5.88 Hz, 3H).

1. temperatureThe reaction mixture was cooled
2. extractionextracted with butanol
3. customThe butanol layer was collected
4. customevaporated to a residue which
5. customwas purified by chromatography (SiO2, elution with 0-20% MeOH in DCM)
6. customto afford the intermediate
7. customThe solvent was evaporated
8. customthe residue was purified by chromatography (SiO2, elution with 0-70% (MeOH/DCM/NH4OH, 13/85/2) in DCM)