Reaction #77508

Reaction equation

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

Solvents

EtOAc

methanol

Conditions

Workup

1. 1
   OtherThe cooled reaction mixture
2. 2
   OtherThe water phase is separated
3. 3
   Extractionextracted twice with EtOAc
4. 4
   DryingThe organic phases are dried (Na2SO4)
5. 5
   Concentrationconcentrated by evaporation
6. 6
   OtherColumn chromatography (SiO2, toluene/EtOAc 2:1→EtOAc/acetone/EtOH 4:4:1→acetone/EtOH 9:1) and crystallisation from hexane

Procedure

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).

Source