2-溴-4-氯-6-甲基苯胺

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Bromo-4-chloro-6-methylaniline (13.2 g, 59.90 mmol) was suspended in 24% hydrochloric acid (40 mL). The stirred mixture was cooled to 0° C. and treated with sodium nitrite (4.54 g, 65.90 mmol) in water (10 mL), dropwise over 30 min. The mixture was then buffered to ca. pH 5 with sodium acetate. This mixture was kept at 0° C. and added in portions to a stirred solution of 2-methyl-2-propanethiol (6.8 mL, 59.9 mmol) in ethanol (40 mL) at 0° C. over 30 min. After the addition, the mixture was stirred at 0° C. for 30 min then transferred to crushed ice, and extracted with ethyl acetate (2×). The organics were pooled together, washed with brine (2×), dried over sodium sulfate, filtered, and concentrated. The resulting residue was dissolved in dimethyl sulfoxide (50 mL) and transferred to a solution of potassium tert-butoxide (53.7 g, 479 mmol) in dimethyl sulfoxide (200 mL) at 0° C. via cannula. The ice-bath was removed and stirring continued for 30 min. The reaction was then poured into a mixture of crushed ice (400 mL) and 10% hydrochloric acid (200 mL) to give a precipitate which was collected by filtration. The resulting solid was triturated with hexanes to afford 7.5 g (54%) as a brown powder. 1H-NMR (CDCl3, 300 MHz) δ 7.97 (s, 1H), 7.60 (s, 1H), 7.44 (s, 1H). Mass spec.: 232.90 (MH)+. was kept at 0° C. After the addition to crushed ice extracted with ethyl acetate (2×) washed with brine (2×) dried over sodium sulfate filtered concentrated The resulting residue was dissolved in dimethyl sulfoxide (50 mL) The ice-bath was removed stirring continued for 30 min The reaction was then poured into a mixture of crushed ice (400 mL) and 10% hydrochloric acid (200 mL) to give a precipitate which was collected by filtration The resulting solid was triturated with hexanes to afford 7.5 g (54%) as a brown powder

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Bromo-4-chloro-6-methylaniline (13.2 g, 59.90 mmol) was suspended in 24% hydrochloric acid (40 mL). The stirred mixture was cooled to 0° C. and treated with sodium nitrite (4.54 g, 65.90 mmol) in water (10 mL), dropwise over 30 min. The mixture was then buffered to ca. pH 5 with sodium acetate. This mixture was kept at 0° C. and added in portions to a stirred solution of 2-methyl-2-propanethiol (6.8 mL, 59.9 mmol) in ethanol (40 mL) at 0° C. over 30 min. After the addition, the mixture was stirred at 0° C. for 30 min then transferred to crushed ice, and extracted with ethyl acetate (2×). The organics were pooled together, washed with brine (2×), dried over sodium sulfate, filtered, and concentrated. The resulting residue was dissolved in dimethyl sulfoxide (50 mL) and transferred to a solution of potassium tert-butoxide (53.7 g, 479 mmol) in dimethyl sulfoxide (200 mL) at 0° C. via cannula. The ice-bath was removed and stirring continued for 30 min. The reaction was then poured into a mixture of crushed ice (400 mL) and 10% hydrochloric acid (200 mL) to give a precipitate which was collected by filtration. The resulting solid was triturated with hexanes to afford 7.5 g (54%) as a brown powder. 1H-NMR (CDCl3, 300 MHz) δ 7.97 (s, 1H), 7.60 (s, 1H), 7.44 (s, 1H). Mass spec.: 232.90 (MH)+. was kept at 0° C. After the addition to crushed ice extracted with ethyl acetate (2×) washed with brine (2×) dried over sodium sulfate filtered concentrated The resulting residue was dissolved in dimethyl sulfoxide (50 mL) The ice-bath was removed stirring continued for 30 min The reaction was then poured into a mixture of crushed ice (400 mL) and 10% hydrochloric acid (200 mL) to give a precipitate which was collected by filtration The resulting solid was triturated with hexanes to afford 7.5 g (54%) as a brown powder

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-Chloro-2-methylaniline (1.0 g, 7.06 mmol), potassium bromide (1.01 g, 8.47 mmol), and ammonium heptamolybdate tetrahydrate (87 mg, 0.07 mmol) were suspended in acetic acid (7 mL, 122 mmol) and cooled to 0° C. The reaction was treated with sodium perborate tetrahydrate (1.2 g, 7.77 mmol), stirred at 0° C. for 30 min, and at room temperature for 2 h. The mixture was poured into water, neutralized with saturated sodium bicarbonate and extracted with ethyl acetate (2×). The organic layers were pooled together, washed with brine (2×), dried over sodium sulfate, and concentrated to afford 1.2 g (78%). 1H-NMR (CDCl3, 500 MHz) δ 7.28 (s, 1H), 6.97 (s, 1H), 4.03 (bs, 2H), 2.17 (s, 3) Mass spec.: 221.90 (MH)+. at room temperature for 2 h extracted with ethyl acetate (2×) washed with brine (2×) dried over sodium sulfate concentrated to afford 1.2 g (78%)

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

实验步骤: 2.20 g (10 mmol) of 2-bromo-4-chloro-6-methyl aniline were dissolved in 125 ml acetic acid. 0.69 g (10 mmol) of sodium nitrite dissolved in 2 ml water were added dropwise. The reaction mixture was stirred at rt for 4 h. Acetic acid was evaporated and the residue dissolved in EtOAc. The organic layer was washed with water, dried over sodium sulfate, filtered and the solvent was evaporated. The residue was several times evaporated with heptane to yield 2.04 g (88%) of 7-bromo-5-chloro-1H-indazol as a light brown solid. 1H NMR (DMSO-d6, 300 MHz): δ 8.23 (s, 1H), 7.91 (s, 1H), 7.67 (s, 1H). were added dropwise Acetic acid was evaporated the residue dissolved in EtOAc The organic layer was washed with water dried over sodium sulfate filtered the solvent was evaporated evaporated with heptane

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

实验步骤: 2.20 g (10 mmol) of 2-bromo-4-chloro-6-methyl aniline were dissolved in 125 ml acetic acid. 0.69 g (10 mmol) of sodium nitrite dissolved in 2 ml water were added dropwise. The reaction mixture was stirred at rt for 4 h. Acetic acid was evaporated and the residue dissolved in EtOAc. The organic layer was washed with water, dried over sodium sulfate, filtered and the solvent was evaporated. The residue was several times evaporated with heptane to yield 2.04 g (88%) of 7-bromo-5-chloro-1H-indazol as a light brown solid. 1H NMR (DMSO-d6, 300 MHz): δ 8.23 (s, 1H), 7.91 (s, 1H), 7.67 (s, 1H). were added dropwise Acetic acid was evaporated the residue dissolved in EtOAc The organic layer was washed with water dried over sodium sulfate filtered the solvent was evaporated evaporated with heptane

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

实验步骤: 2.83 g (20 mmol) of 4-chloro-2-methyl aniline and 1.74 g (22 mmol) of pyridine were dissolved in 20 ml DCM. 3.20 g (20 mmol) of bromine were added dropwise under cooling. The reaction mixture was stirred for 2 h at rt. The solvent was removed and the residue was dissolved in diethyl ether. The organic layer was washed with water, dried over sodium sulfate, filtered and the solvent was evaporated. The crude product was purified by column chromatography (silica gel; diethyl ether/heptane 1:1) to yield 3.91 g (89%) of 2-bromo-4-chloro-6-methyl aniline as a light green solid. 1H NMR (CDCl3, 300 MHz): δ 7.30 (s, 1H), 6.99 (s, 1H), 4.04 (br s, 2H), 2.19 (s, 3H). under cooling The solvent was removed the residue was dissolved in diethyl ether The organic layer was washed with water dried over sodium sulfate filtered the solvent was evaporated The crude product was purified by column chromatography (silica gel; diethyl ether/heptane 1:1)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Bromo-4-chloro-6-methylaniline (13.2 g, 59.90 mmol) was suspended in 24% hydrochloric acid (40 mL). The stirred mixture was cooled to 0° C. and treated with sodium nitrite (4.54 g, 65.90 mmol) in water (10 mL), dropwise over 30 min. The mixture was then buffered to ca. pH 5 with sodium acetate. This mixture was kept at 0° C. and added in portions to a stirred solution of 2-methyl-2-propanethiol (6.8 mL, 59.9 mmol) in ethanol (40 mL) at 0° C. over 30 min. After the addition, the mixture was stirred at 0° C. for 30 min then transferred to crushed ice, and extracted with ethyl acetate (2×). The organics were pooled together, washed with brine (2×), dried over sodium sulfate, filtered, and concentrated. The resulting residue was dissolved in dimethyl sulfoxide (50 mL) and transferred to a solution of potassium tert-butoxide (53.7 g, 479 mmol) in dimethyl sulfoxide (200 mL) at 0° C. via cannula. The ice-bath was removed and stirring continued for 30 min. The reaction was then poured into a mixture of crushed ice (400 mL) and 10% hydrochloric acid (200 mL) to give a precipitate which was collected by filtration. The resulting solid was triturated with hexanes to afford 7.5 g (54%) as a brown powder. 1H-NMR (CDCl3, 300 MHz) δ 7.97 (s, 1H), 7.60 (s, 1H), 7.44 (s, 1H). Mass spec.: 232.90 (MH)+. was kept at 0° C. After the addition to crushed ice extracted with ethyl acetate (2×) washed with brine (2×) dried over sodium sulfate filtered concentrated The resulting residue was dissolved in dimethyl sulfoxide (50 mL) The ice-bath was removed stirring continued for 30 min The reaction was then poured into a mixture of crushed ice (400 mL) and 10% hydrochloric acid (200 mL) to give a precipitate which was collected by filtration The resulting solid was triturated with hexanes to afford 7.5 g (54%) as a brown powder

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-Chloro-2-methylaniline (1.0 g, 7.06 mmol), potassium bromide (1.01 g, 8.47 mmol), and ammonium heptamolybdate tetrahydrate (87 mg, 0.07 mmol) were suspended in acetic acid (7 mL, 122 mmol) and cooled to 0° C. The reaction was treated with sodium perborate tetrahydrate (1.2 g, 7.77 mmol), stirred at 0° C. for 30 min, and at room temperature for 2 h. The mixture was poured into water, neutralized with saturated sodium bicarbonate and extracted with ethyl acetate (2×). The organic layers were pooled together, washed with brine (2×), dried over sodium sulfate, and concentrated to afford 1.2 g (78%). 1H-NMR (CDCl3, 500 MHz) δ 7.28 (s, 1H), 6.97 (s, 1H), 4.03 (bs, 2H), 2.17 (s, 3) Mass spec.: 221.90 (MH)+. at room temperature for 2 h extracted with ethyl acetate (2×) washed with brine (2×) dried over sodium sulfate concentrated to afford 1.2 g (78%)

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

实验步骤: 2.20 g (10 mmol) of 2-bromo-4-chloro-6-methyl aniline were dissolved in 125 ml acetic acid. 0.69 g (10 mmol) of sodium nitrite dissolved in 2 ml water were added dropwise. The reaction mixture was stirred at rt for 4 h. Acetic acid was evaporated and the residue dissolved in EtOAc. The organic layer was washed with water, dried over sodium sulfate, filtered and the solvent was evaporated. The residue was several times evaporated with heptane to yield 2.04 g (88%) of 7-bromo-5-chloro-1H-indazol as a light brown solid. 1H NMR (DMSO-d6, 300 MHz): δ 8.23 (s, 1H), 7.91 (s, 1H), 7.67 (s, 1H). were added dropwise Acetic acid was evaporated the residue dissolved in EtOAc The organic layer was washed with water dried over sodium sulfate filtered the solvent was evaporated evaporated with heptane

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

实验步骤: 2.83 g (20 mmol) of 4-chloro-2-methyl aniline and 1.74 g (22 mmol) of pyridine were dissolved in 20 ml DCM. 3.20 g (20 mmol) of bromine were added dropwise under cooling. The reaction mixture was stirred for 2 h at rt. The solvent was removed and the residue was dissolved in diethyl ether. The organic layer was washed with water, dried over sodium sulfate, filtered and the solvent was evaporated. The crude product was purified by column chromatography (silica gel; diethyl ether/heptane 1:1) to yield 3.91 g (89%) of 2-bromo-4-chloro-6-methyl aniline as a light green solid. 1H NMR (CDCl3, 300 MHz): δ 7.30 (s, 1H), 6.99 (s, 1H), 4.04 (br s, 2H), 2.19 (s, 3H). under cooling The solvent was removed the residue was dissolved in diethyl ether The organic layer was washed with water dried over sodium sulfate filtered the solvent was evaporated The crude product was purified by column chromatography (silica gel; diethyl ether/heptane 1:1)