3-bromo-4-ethylaniline

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromo-1-ethyl-4-nitro-benzene (25 g, 0.019 mol) in MeOH (100 mL) was added Raney-Ni (2.5 g). The reaction mixture was hydrogenated under hydrogen (1 atm) at room temperature. After stirring for 3 hours, the mixture was filtered and concentrated under reduced pressure. The crude material was purified by preparative HPLC to give 3-bromo-4-ethylaniline (8.0 g, 48%). 1H NMR (400 MHz, CDCl3) δ 6.92 (d, J=8.4 Hz, 1H), 6.83 (d, J=2.4 Hz, 1H), 6.52 (dd, J=2.4, 8.4 Hz, 1H), 2.57 (q, J=7.6 Hz, 2H), 1.10 (t, J=7.6 Hz, 3H). MS (ESI) m/e (M+H+) 200. was hydrogenated under hydrogen (1 atm) at room temperature the mixture was filtered concentrated under reduced pressure The crude material was purified by preparative HPLC

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a manner similar to that of Example 1(d), by reacting 27 g (135 mmol) of 3-bromo-4-ethylphenylamine with 11 g (162 mmol) of sodium nitrite, and after purification by chromatography on a column of silica eluted with a mixture of heptane and ethyl acetate (90/10), 13 g (49%) of the expected product are obtained in the form of a brown oil. after purification by chromatography on a column of silica eluted with a mixture of heptane and ethyl acetate (90/10), 13 g (49%) of the expected product are obtained in the form of a brown oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a manner similar to that of Example 1(d), by reacting 27 g (135 mmol) of 3-bromo-4-ethylphenylamine with 11 g (162 mmol) of sodium nitrite, and after purification by chromatography on a column of silica eluted with a mixture of heptane and ethyl acetate (90/10), 13 g (49%) of the expected product are obtained in the form of a brown oil. after purification by chromatography on a column of silica eluted with a mixture of heptane and ethyl acetate (90/10), 13 g (49%) of the expected product are obtained in the form of a brown oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a manner similar to that of Example 1(c), by reacting 34 g (148 mmol) of 1-bromo-2-ethyl-5-nitrobenzene with 33 g (591 mmol) of iron, and after purification by chromatography on a column of silica eluted with a mixture of heptane and ethyl acetate (90/10), 27 g (89%) of the expected product are obtained in the form of a yellow oil. after purification by chromatography on a column of silica eluted with a mixture of heptane and ethyl acetate (90/10), 27 g (89%) of the expected product are obtained in the form of a yellow oil

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

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

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hydrogenation of 4.45 g (19 mmol) of 3-bromo-4-ethyl-nitrobenzene (for preparation see Macromolecules 1995, 28, 5618) in 100 ml of ethanol in the presence of 1 g of Raney nickel, followed by filtration, concentration by evaporation and chromatography (SiO2; methylenechloride), yields 3-bromo-4-ethyl-aniline; 1H NMR (CDCl3) δ6.94 (d, 1H), 6.82 (s, 1H), 6.50 (d, 1H), 3.50 (s, H2N), 2.57 (q, 2H), 1.10 (t, 3H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromo-1-ethyl-4-nitro-benzene (25 g, 0.019 mol) in MeOH (100 mL) was added Raney-Ni (2.5 g). The reaction mixture was hydrogenated under hydrogen (1 atm) at room temperature. After stirring for 3 hours, the mixture was filtered and concentrated under reduced pressure. The crude material was purified by preparative HPLC to give 3-bromo-4-ethylaniline (8.0 g, 48%). 1H NMR (400 MHz, CDCl3) δ 6.92 (d, J=8.4 Hz, 1H), 6.83 (d, J=2.4 Hz, 1H), 6.52 (dd, J=2.4, 8.4 Hz, 1H), 2.57 (q, J=7.6 Hz, 2H), 1.10 (t, J=7.6 Hz, 3H). MS (ESI) m/e (M+H+) 200. was hydrogenated under hydrogen (1 atm) at room temperature the mixture was filtered concentrated under reduced pressure The crude material was purified by preparative HPLC

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

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

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hydrogenation of 4.45 g (19 mmol) of 3-bromo-4-ethyl-nitrobenzene (for preparation see Macromolecules 1995, 28, 5618) in 100 ml of ethanol in the presence of 1 g of Raney nickel, followed by filtration, concentration by evaporation and chromatography (SiO2; methylenechloride), yields 3-bromo-4-ethyl-aniline; 1H NMR (CDCl3) δ6.94 (d, 1H), 6.82 (s, 1H), 6.50 (d, 1H), 3.50 (s, H2N), 2.57 (q, 2H), 1.10 (t, 3H).