反应详情

Under a N2 atmosphere, 2.04 g (5.17 mmol) of an (E/Z) mixture of 2-iodo-benzoic acid-[3-(6-methoxy-pyridin-3-yl)-allylamide], 1.53 g (5.17 mmol) of tetra-butylammonium chloride and 22 mg (0.1 mmol) of palladium diacetate are dissolved in 80 ml of DMF, then 1.8 ml (12.9 mmol) of trethylamine are added and stirring effected for 2 days at 110° C. Filtration is carried out, and the DMF is partially evaporated on a RE. The residue is dissolved with EtOAc and diluted Na2CO3 solution, the water phase separated and extraction effected twice more with EtOAc. The organic phases are washed twice with water and brine, dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2, methylene chloride/acetone 3:1), concentration by evaporation and stirring in petroleum ether yield 4-[(6-methoxy-pyridin-3-yl)-methyl]-2H-isoquinolin-1-one; m.p. 191° C.; HPLC(gradient20-100) tRef=13.0.

1. addition1.8 ml (12.9 mmol) of trethylamine are added
2. filtrationFiltration
3. customthe DMF is partially evaporated on a RE
4. dissolutionThe residue is dissolved with EtOAc and diluted Na2CO3 solution
5. customthe water phase separated
6. extractionextraction
7. washThe organic phases are washed twice with water and brine
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated by evaporation
10. concentrationColumn chromatography (SiO2, methylene chloride/acetone 3:1), concentration
11. customby evaporation
12. stirringstirring in petroleum ether