4-Bromo-3-methoxyphenylene-1,2-diamine

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 1 L four-necked round bottom flask fitted with a magnetic stirrer was dried and cooled under a stream of nitrogen then charged with 4-bromo-3-methoxy-benzene-1,2-diamine (61 g, 0.28 mol, 1.0 equiv.) in formic acid (200 mL). The reaction mixture was heated at 100° C. for 2 h, cooled and quenched with ice water (1 L). The reaction mixture was basified with 10% NaOH solution and extracted with ethyl acetate (2×1000 mL). The separated organic layers were combined, washed with brine solution (750 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude material was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (30-50% EtOAc) to afford 6-bromo-7-methoxy-1H-benzoimidazole (36 g, crude) as a brown solid. 1H NMR (300 MHz, DMSO-d6): δ 4.26 (br, 3H), 7.16 (s, 1H), 7.29-7.32 (d, 1H), 8.19 (s, 1H), 12.67 (br, 1H). A 1 L four-necked round bottom flask fitted with a magnetic stirrer was dried cooled under a stream of nitrogen cooled quenched with ice water (1 L) extracted with ethyl acetate (2×1000 mL) washed with brine solution (750 mL) dried (Na2SO4) filtered concentrated in vacuo The crude material was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (30-50% EtOAc)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 2 L Parr shaker bottle was dried and cooled under a stream of nitrogen then charged with 5-bromo-4-methoxybenzofurazanoxide (100 g, 0.44 mol, 1.0 equiv.) in EtOAc (1 L) and 10% Pd/C (10% w/w, 10.0 g) was added. The reaction was then stirred at RT overnight under hydrogen. The reaction mixture was filtered through a Celite® pad and concentrated in vacuo to afford 4-bromo-3-methoxy-benzene-1,2-diamine (61.0 g, crude) as a dark brown semi solid. The crude material was taken directly to the next step. A 2 L Parr shaker bottle was dried cooled under a stream of nitrogen was added The reaction mixture was filtered through a Celite® pad concentrated in vacuo

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 1 L four-necked round bottom flask fitted with a magnetic stirrer was dried and cooled under a stream of nitrogen then charged with 4-bromo-3-methoxy-benzene-1,2-diamine (61 g, 0.28 mol, 1.0 equiv.) in formic acid (200 mL). The reaction mixture was heated at 100° C. for 2 h, cooled and quenched with ice water (1 L). The reaction mixture was basified with 10% NaOH solution and extracted with ethyl acetate (2×1000 mL). The separated organic layers were combined, washed with brine solution (750 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude material was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (30-50% EtOAc) to afford 6-bromo-7-methoxy-1H-benzoimidazole (36 g, crude) as a brown solid. 1H NMR (300 MHz, DMSO-d6): δ 4.26 (br, 3H), 7.16 (s, 1H), 7.29-7.32 (d, 1H), 8.19 (s, 1H), 12.67 (br, 1H). A 1 L four-necked round bottom flask fitted with a magnetic stirrer was dried cooled under a stream of nitrogen cooled quenched with ice water (1 L) extracted with ethyl acetate (2×1000 mL) washed with brine solution (750 mL) dried (Na2SO4) filtered concentrated in vacuo The crude material was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (30-50% EtOAc)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 2 L Parr shaker bottle was dried and cooled under a stream of nitrogen then charged with 5-bromo-4-methoxybenzofurazanoxide (100 g, 0.44 mol, 1.0 equiv.) in EtOAc (1 L) and 10% Pd/C (10% w/w, 10.0 g) was added. The reaction was then stirred at RT overnight under hydrogen. The reaction mixture was filtered through a Celite® pad and concentrated in vacuo to afford 4-bromo-3-methoxy-benzene-1,2-diamine (61.0 g, crude) as a dark brown semi solid. The crude material was taken directly to the next step. A 2 L Parr shaker bottle was dried cooled under a stream of nitrogen was added The reaction mixture was filtered through a Celite® pad concentrated in vacuo