反应详情

温度

120 °C

In a pressure tube was charged with 3-(5-chloro-6-fluoropyridin-2-yl)-5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine (103.4 mg, 0.2268 mmol), 4-(N-Boc-amino)-piperidine (136.24 mg, 0.6803 mmol), 4-Methylmorpholine (249.30 uL, 10 mmol), and N-Methylpyrrolidinone (3 mL). The mixture was heated at 120° C. overnight. The reaction mixture was cooled to room temperature, diluted with EtOAc, washed 3 times with water. The organic layer was dried with MgSO4, and then concentrated. The residue was purified on silica eluted with 0 to 100% EtOAc in DCM to afford tert-butyl 1-(3-chloro-6-(5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperidin-4-ylcarbamate. It was dissolved in 1,4-Dioxane (5 mL) and treated with 4.0 M of Hydrogen chloride in 1,4-Dioxane (5 mL) overnight. The mixture was concentrated, and the residue was purified by reverse phase HPLC to afford 241 as an off-white solid (8.7 mg, 19%). 1H NMR (400 MHz, DMSO) δ 9.24 (d, J=10.3 Hz, 2H), 8.99 (s, 1H), 8.61 (s, 1H), 8.42 (d, J=7.5 Hz, 1H), 7.89 (d, J=8.1 Hz, 1H), 7.77 (d, J=8.1 Hz, 1H), 7.56 (d, J=4.4 Hz, 1H), 3.99 (d, J=12.0 Hz, 2H), 3.09 (d, J=12.4 Hz, 3H), 1.94 (d, J=11.6 Hz, 2H), 1.56 (d, J=11.1 Hz, 2H). ESI MS m/z=406.1 (M+1)

1. temperatureThe reaction mixture was cooled to room temperature
2. washwashed 3 times with water
3. dry with materialThe organic layer was dried with MgSO4
4. concentrationconcentrated
5. customThe residue was purified on silica
6. washeluted with 0 to 100% EtOAc in DCM