反应详情

温度

140 °C

To a sealed tube charged with 6-bromo-2-[2-(4-cyclobutylpiperazin-1-yl)-2-oxoethyl]-1,2,3,4-tetrahydroisoquinoline (128 mg, 0.326 mmol), CuCl (3.2 mg, 0.0163 mmol, 0.05 eq.), pyridazin-3(2H)-one (47 mg, 0.489 mmol, 1.5 eq.), 8-hydroxyquinoline (9.5 mg, 0.0326 mmol, 0.1 eq.) and K2CO3 (90 mg, 0.652 mmol, 2.0 eq.) is added anhydrous DMF (3 ml). The mixture is degassed with nitrogen for 5 min. The tube is sealed and heated at 140° C. overnight. The mixture is cooled to rt and filtered through Celite. The Celite bed is washed with EtOAc, the combined organics are concentrated, and 5N HCl (30 mL) is added. The mixture is extracted with EtOAc (2×30 mL). The aqueous layer is basified with 10N NaOH, and extracted with DCM (3×40 mL), and the combined organics are dried and concentrated. The crude reaction mixture is purified by preparatory LC/MS to yield the title compound. 1H NMR (300 MHz, CDCl3) δ 7.87 (1H, dd), 7.32 (2H, m), 7.24 (1H, d), 7.12 (1H, d), 7.04 (1H, d), 3.72 (2H, s), 3.67-3.63 (4H, m), 3.36 (2H, s), 2.94 (2H, t), 2.81 (2H, t), 2.69 (1H, m), 2.27 (4H, m), 1.66-2.08 (6H); MS (+VE) m/z 408.14 (M++1).

1. customThe mixture is degassed with nitrogen for 5 min
2. customThe tube is sealed
3. temperatureThe mixture is cooled to rt
4. filtrationfiltered through Celite
5. washThe Celite bed is washed with EtOAc
6. concentrationthe combined organics are concentrated
7. addition5N HCl (30 mL) is added
8. extractionThe mixture is extracted with EtOAc (2×30 mL)
9. extractionextracted with DCM (3×40 mL)
10. customthe combined organics are dried
11. concentrationconcentrated
12. customThe crude reaction mixture
13. customis purified by preparatory LC/MS