反応 #77508

反応方程式

5-chloro-8-[(6-methoxy-pyridin-3-yl)-methyl]-[1,6]naphthyridine

3-bromo-4-ethyl-aniline

HCl dioxane

Na2CO3

→

5-(3-bromo-4-ethyl-anilino)-8-[(6-methoxy-pyridin-3-yl)-methyl]-[1,6]naphthyridine

5-(3-bromo-4-ethyl-anilino)-8-[(6-hydroxy-pyridin-3-yl)-methyl]-[1,6]naphthyridine

溶媒

EtOAc

methanol

反応条件

後処理

1. 1
   その他The cooled reaction mixture
2. 2
   その他The water phase is separated
3. 3
   抽出extracted twice with EtOAc
4. 4
   乾燥The organic phases are dried (Na2SO4)
5. 5
   濃縮concentrated by evaporation
6. 6
   その他Column chromatography (SiO2, toluene/EtOAc 2:1→EtOAc/acetone/EtOH 4:4:1→acetone/EtOH 9:1) and crystallisation from hexane

実験手順

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).

出典