2-(2-amino-4-bromo-N-methylanilino)ethanol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-((2-amino-4-bromophenyl)(methyl)amino)ethanol (3.09 g, 0.013 mol) was dissolved in DCM (100 mL) with DMF (10 drop), Thionyl chloride (1.8 g, 0.015 mol in 10 ml DCM) was added dropwise at 0° C. The reaction was stirred at rt for 10 min then 80° C. for 30 min, rt for 16 h. The mixture was partitioned between 1N NaOH and DCM (2×30 ml). The combined organic layers was concentrated to give 3.2 g, (96.3%) of 4-bromo-N1-(2-chloroethyl)-N1-methylbenzene-1,2-diamine LCMS-ESI+ (m/z): [M+H]+ calcd for C9H12BrClN2:261.99; found 262.9. was added dropwise at 0° C 80° C. for 30 min rt for 16 h The mixture was partitioned between 1N NaOH and DCM (2×30 ml) The combined organic layers was concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-((4-bromo-2-nitrosophenyl)(methyl)amino)ethanol (6.5 g, 0.025 mol) was dissolved in THF (100 ml), Sodium hydrosulfite (26.2 g, 0.15 mol in water 150 mL) was added. The reaction was stirred at rt for 1 h. The mixture was extracted with EtOAc (2×100 ml). The combined organic layers was concentrated and purified by flash chromatography eluted with EtOAc to give 3.1 g, (50.3%) of 2-((2-amino-4-bromophenyl)(methyl)amino)ethanol LCMS-ESI+ (m/z): [M+H]+ calcd for C9H13BrN2O4:244.03; found 244.96, 246.91. The mixture was extracted with EtOAc (2×100 ml) The combined organic layers was concentrated purified by flash chromatography eluted with EtOAc

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-((4-bromo-2-nitrosophenyl)(methyl)amino)ethanol (6.5 g, 0.025 mol) was dissolved in THF (100 ml), Sodium hydrosulfite (26.2 g, 0.15 mol in water 150 mL) was added. The reaction was stirred at rt for 1 h. The mixture was extracted with EtOAc (2×100 ml). The combined organic layers was concentrated and purified by flash chromatography eluted with EtOAc to give 3.1 g, (50.3%) of 2-((2-amino-4-bromophenyl)(methyl)amino)ethanol LCMS-ESI+ (m/z): [M+H]+ calcd for C9H13BrN2O4:244.03; found 244.96, 246.91. The mixture was extracted with EtOAc (2×100 ml) The combined organic layers was concentrated purified by flash chromatography eluted with EtOAc

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-((4-bromo-2-nitrosophenyl)(methyl)amino)ethanol (6.5 g, 0.025 mol) was dissolved in THF (100 ml), Sodium hydrosulfite (26.2 g, 0.15 mol in water 150 mL) was added. The reaction was stirred at rt for 1 h. The mixture was extracted with EtOAc (2×100 ml). The combined organic layers was concentrated and purified by flash chromatography eluted with EtOAc to give 3.1 g, (50.3%) of 2-((2-amino-4-bromophenyl)(methyl)amino)ethanol LCMS-ESI+ (m/z): [M+H]+ calcd for C9H13BrN2O4:244.03; found 244.96, 246.91. The mixture was extracted with EtOAc (2×100 ml) The combined organic layers was concentrated purified by flash chromatography eluted with EtOAc

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Thionylchloride (0.78 g, 6.74 mmol) was added dropwise to a solution of 2-((2-amino-4-bromophenyl)(methyl)amino)ethanol (25C) (1.376 g, 5.62 mmol) in DCM (50 mL) and DMF (10 drops) at 0° C. The mixture was allowed to warm up to rt and stirred for 1 hour. Then, the mixture was heated to 35° C. for 2.5 hours, concentrated, diluted with 1N NaOH, and extracted with DCM. The organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash column chromatography on silica gel eluting with a gradient of PE:EtOAc 100:0-85:15, to provide 0.611 g (41%) of the desired product 4-bromo-N1-(2-chloroethyl)-N1-methylbenzene-1,2-diamine (25D): 1H NMR (300 MHz, CDCl3) δ 6.88-6.79 (3H, m), 4.20 (2H, bs), 3.56 (2H, t), 3.17 (2H, t), 2.67 (3H, s). Then, the mixture was heated to 35° C. for 2.5 hours concentrated diluted with 1N NaOH extracted with DCM The organic phases were washed with brine dried over Na2SO4 filtered concentrated under reduced pressure The crude material was purified by flash column chromatography on silica gel eluting with a gradient of PE

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Iron (1.5 g, 26.2 mmol) and ammonium chloride (0.39 g, 1.0 eq) in water (8 mL) was heated to reflux for 0.5 hours, 2-((4-bromo-2-nitrophenyl)(methyl)amino)ethanol (25B) (2.0 g, 7.27 mmol) was slowly added. The reaction mixture was heated to reflux for 14 hours, cooled to rt, diluted with water and EtOAc and filtered through Celite. The aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel eluting with a gradient of PE:EtOAc 60:40-40:60, to provide 1.36 g (76%) of the desired product 2-((2-amino-4-bromophenyl)(methyl)amino)ethanol (25C): 1H NMR (300 MHz, CDCl3) δ 6.92-6.82 (3H, m), 3.68 (2H, t), 3.04 (2H, t), 2.70 (3H, s). to reflux for 0.5 hours The reaction mixture was heated to reflux for 14 hours filtered through Celite The aqueous phase was extracted with EtOAc The combined organic phases were washed with brine dried over Na2SO4 filtered concentrated under reduced pressure The crude material was purified by column chromatography on silica gel eluting with a gradient of PE

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Thionyichloride (0.78 g, 6.74 mmol) was added dropwise to a solution of 2-((2-amino-4-bromophenyl)(methyl)amino)ethanol (25C) (1.376 g, 5.62 mmol) in DCM (50 mL) and DMF (10 drops) at 0° C. The mixture was allowed to warm up to rt and stirred for 1 hour. Then, the mixture was heated to 35° C. for 2.5 hours, concentrated, diluted with 1N NaOH, and extracted with DCM. The organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash column chromatography on silica gel eluting with a gradient of PE:EtOAc 100:0-85:15, to provide 0.611 g (41%) of the desired product 4-bromo-N1-(2-chloroethyl)-N1-methylbenzene-1,2-diamine (25D): 1H NMR (300 MHz, CDCl3) δ 6.88-6.79 (3H, m), 4.20 (2H, bs), 3.56 (2H, t), 3.17 (2H, t), 2.67 (3H, s). Then, the mixture was heated to 35° C. for 2.5 hours concentrated diluted with 1N NaOH extracted with DCM The organic phases were washed with brine dried over Na2SO4 filtered concentrated under reduced pressure The crude material was purified by flash column chromatography on silica gel eluting with a gradient of PE

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Iron (1.5 g, 26.2 mmol) and ammonium chloride (0.39 g, 1.0 eq) in water (8 mL) was heated to reflux for 0.5 hours. 2-((4-bromo-2-nitrophenyl)(methyl)amino)ethanol (25B) (2.0 g, 7.27 mmol) was slowly added. The reaction mixture was heated to reflux for 14 hours, cooled to rt, diluted with water and EtOAc and filtered through Celite. The aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel eluting with a gradient of PE:EtOAc 60:40-40:60, to provide 1.36 g (76%) of the desired product 2-((2-amino-4-bromophenyl)(methyl)amino)ethanol (25C): 1H NMR (300 MHz, CDCl3) δ 6.92-6.82 (3H, m), 3.68 (2H, t), 3.04 (2H, t), 2.70 (3H, s). to reflux for 0.5 hours The reaction mixture was heated to reflux for 14 hours filtered through Celite The aqueous phase was extracted with EtOAc The combined organic phases were washed with brine dried over Na2SO4 filtered concentrated under reduced pressure The crude material was purified by column chromatography on silica gel eluting with a gradient of PE

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Thionylchloride (0.78 g, 6.74 mmol) was added dropwise to a solution of 2-((2-amino-4-bromophenyl)(methyl)amino)ethanol (25C) (1.376 g, 5.62 mmol) in DCM (50 mL) and DMF (10 drops) at 0° C. The mixture was allowed to warm up to rt and stirred for 1 hour. Then, the mixture was heated to 35° C. for 2.5 hours, concentrated, diluted with 1N NaOH, and extracted with DCM. The organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash column chromatography on silica gel eluting with a gradient of PE:EtOAc 100:0-85:15, to provide 0.611 g (41%) of the desired product 4-bromo-N1-(2-chloroethyl)-N1-methylbenzene-1,2-diamine (25D): 1H NMR (300 MHz, CDCl3) δ 6.88-6.79 (3H, m), 4.20 (2H, bs), 3.56 (2H, t), 3.17 (2H, t), 2.67 (3H, s). Then, the mixture was heated to 35° C. for 2.5 hours concentrated diluted with 1N NaOH extracted with DCM The organic phases were washed with brine dried over Na2SO4 filtered concentrated under reduced pressure The crude material was purified by flash column chromatography on silica gel eluting with a gradient of PE

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Iron (1.5 g, 26.2 mmol) and ammonium chloride (0.39 g, 1.0 eq) in water (8 mL) was heated to reflux for 0.5 hours. 2-((4-bromo-2-nitrophenyl)(methyl)amino)ethanol (25B) (2.0 g, 7.27 mmol) was slowly added. The reaction mixture was heated to reflux for 14 hours, cooled to rt, diluted with water and EtOAc and filtered through Celite. The aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel eluting with a gradient of PE:EtOAc 60:40-40:60, to provide 1.36 g (76%) of the desired product 2-((2-amino-4-bromophenyl)(methyl)amino)ethanol (25C): 1H NMR (300 MHz, CDCl3) δ 6.92-6.82 (3H, m), 3.68 (2H, t), 3.04 (2H, t), 2.70 (3H, s). to reflux for 0.5 hours The reaction mixture was heated to reflux for 14 hours filtered through Celite The aqueous phase was extracted with EtOAc The combined organic phases were washed with brine dried over Na2SO4 filtered concentrated under reduced pressure The crude material was purified by column chromatography on silica gel eluting with a gradient of PE