反应详情

温度

80 °C

To a solution of 2-[6-bromo-1-(2-chloro-phenyl)-3,4-dihydro-1H-isoquinolin-2-yl]-1-(4-cyclobutyl-piperazin-1-yl)-ethanone (310 mg, 0.62 mmol) in dry DMF (5.0 ml) is added n-butylvinyl ether (310 mg, 3.98 mmol, 5.0 eq.), TEA (75 mg, 0.74 mmol, 1.2 eq.), 1,3-bis(diphenylphosphino)propane (7 mg, 0.0017 mmol, 0.0276 eq.), and palladium acetate (3.5 mg, 0.015 mmol, 0.025 eq.) under nitrogen. The resulting mixture is stirred at 80° C. for 7 hr. Water (20 ml) is added to quench the reaction, and the mixture is extracted with EtOAc (10 ml×3). The combined organic phase is washed with water, and treated with concentrated HCl (1.0 ml). The mixture is stirred at rt for 2 hr, and then basified with saturated sodium carbonate solution. The organic phase is collected, and the aqueous phase is extracted with EtOAc (10 ml×2). The combined organic phase is dried over sodium sulfate, and concentrated. The residue is purified by PTLC (EtOAc/4% TEA) to give the title compound. 1H NMR (300 MHz, CDCl3) δ 7.74 (1H, s), 7.59 (1H, dd), 7.41 (1H, dd), 7.10˜7.25 (3H, m), 6.72 (1H, d), 5.22 (1H, s), 3.81 (1H, m), 3.04˜3.52 (7H, m), 2.78˜2.98 (2H, m), 2.67 (1H, m), 2.55 (3H, s), 2.41 (1H, m), 2.27 (1H, m), 1.96˜2.14 (4H), 1.60˜1.92 (4H); MS (+VE) m/z 466.00 (M+).

1. customto quench
2. customthe reaction
3. extractionthe mixture is extracted with EtOAc (10 ml×3)
4. washThe combined organic phase is washed with water
5. additiontreated with concentrated HCl (1.0 ml)
6. stirringThe mixture is stirred at rt for 2 hr
7. customThe organic phase is collected
8. extractionthe aqueous phase is extracted with EtOAc (10 ml×2)
9. dry with materialThe combined organic phase is dried over sodium sulfate
10. concentrationconcentrated
11. customThe residue is purified by PTLC (EtOAc/4% TEA)