反应详情

温度

150 °C

A mixture of Example 7a (0.100 g, 0.247 mmol), tert-butyl 4-carbamoylpiperidine-1-carboxylate (0.0960 g, 0.421 mmol), cesium carbonate (0.105 g, 0.322 mmol), palladium (II) acetate (2.8 mg, 0.012 mmol), and Xantphos (10.7 mg, 0.019 mmol) in dioxane (3 mL) and DMF (0.1 mL) was degassed and heated at 150° C. for 30 minutes in a Biotage microwave reactor. The solvent was evaporated. The residue was treated with 20% brine and extracted with EtOAc. The organic layer was concentrated, dissolved in dioxane (2.5 mL), and treated with 20% sodium hydroxide (0.50 mL, 0.247 mmol). The mixture was heated at 50° C. for 2 hours. After concentration, the residue was triturated with water and filtered. The solid was purified by reverse-phase HPLC as described in Example 56 to give the title compound (12.7 mg) as trifluoroacetic acid salts. 1H NMR (500 MHz, METHANOL-d4) ppm 1.81-2.07 (m, 2H), 2.10-2.23 (m, 2H), 2.84 (m, 1H), 3.01-3.15 (m, 2H), 3.45-3.57 (m, 2H), 7.30 (dd, J=7.93, 4.88 Hz, 1H), 7.48 (d, J=1.22 Hz, 1H), 8.04 (s, 1H), 8.32 (dd, J=4.73, 1.37 Hz, 1H), 8.48 (dd, J=8.09, 1.37 Hz, 1H), 8.54 (s, 1H). MS (ESI+) m/z 356.0 (M+H)+.

1. customThe solvent was evaporated
2. additionThe residue was treated with 20% brine
3. extractionextracted with EtOAc
4. concentrationThe organic layer was concentrated
5. dissolutiondissolved in dioxane (2.5 mL)
6. temperatureThe mixture was heated at 50° C. for 2 hours
7. concentrationAfter concentration
8. customthe residue was triturated with water
9. filtrationfiltered
10. customThe solid was purified by reverse-phase HPLC