反应详情

温度

80 °C

Under a N2 atmosphere, 241 mg (0.84 mmol) of 5-chloro-8-[(6-methoxy-pyridin-3-yl)-methyl]-[1,6]naphthyridine in 4 ml of methanol are mixed with 252 mg (1.26 mmol) of 3-bromo-4-ethyl-aniline (Ex. 9) and 0.21 ml of 4 N HCl/dioxane and stirred for 16 h at 80° C. The cooled reaction mixture is taken up with diluted Na2CO3 solution and EtOAc. The water phase is separated and extracted twice with EtOAc. The organic phases are dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2, toluene/EtOAc 2:1→EtOAc/acetone/EtOH 4:4:1→acetone/EtOH 9:1) and crystallisation from hexane yield 5-(3-bromo-4-ethyl-anilino)-8-[(6-methoxy-pyridin-3-yl)-methyl]-[1,6]naphthyridine 37a (m.p. 142-146° C.; FAB-MS: (M+H)+=449/451; HPLC(gradient20-100) tRet=10.9) and 5-(3-bromo-4-ethyl-anilino)-8-[(6-hydroxy-pyridin-3-yl)-methyl]-[1,6]naphthyridine 37b (m.p. 262-265° C.; FAB-MS: (M+H)+=435/437; HPLC(gradient20-100) tRet=9.3).

1. customThe cooled reaction mixture
2. customThe water phase is separated
3. extractionextracted twice with EtOAc
4. dry with materialThe organic phases are dried (Na2SO4)
5. concentrationconcentrated by evaporation
6. customColumn chromatography (SiO2, toluene/EtOAc 2:1→EtOAc/acetone/EtOH 4:4:1→acetone/EtOH 9:1) and crystallisation from hexane