4-bromo-3,5-dichloroaniline

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

実験手順: The title compound was prepared as described in Example 159 substituting 4-bromo-3,5-dichloroaniline and (4-chlorophenyl)boronic acid for 4-bromo-3-chloroaniline and (4-(trifluoromethyl)phenyl)boronic acid, respectively.

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 100 g of 4-bromo-3,5-dichlorophenylamine are added with stirring at 5° C. to a mixture of 125 ml of water and 90 ml of concentrated sulphuric acid. 230 g of crushed ice are added to the reaction mixture, followed by 29 g of sodium nitrite in 70 ml of water, and the reaction mixture is left stirring for 15 minutes. The reaction mixture is added rapidly to a mixture composed of 280 ml of concentrated sulphuric acid and 200 ml of water raised to 160° C., and the reaction mixture is left stirring at 160° C. for 1 hour. The reaction mixture is poured onto a water/crushed ice mixture and extracted with dichloromethane. The organic phase is dried over magnesium sulphate and the solvents are evaporated off under reduced pressure. The residue obtained is purified by chromatography on a column of silica gel, eluting with a 4/6 (v/v) cyclohexane/dichloromethane mixture. the reaction mixture is left The reaction mixture is added rapidly to a mixture the reaction mixture is left stirring at 160° C. for 1 hour crushed ice mixture extracted with dichloromethane The organic phase is dried over magnesium sulphate the solvents are evaporated off under reduced pressure The residue obtained is purified by chromatography on a column of silica gel eluting with a 4/6 (v/v) cyclohexane/dichloromethane mixture

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

実験手順: 202 g of N-(4-bromo-3,5-dichlorophenyl)acetamide and 220 g of sodium hydroxide (as an aqueous 50% solution) in 670 ml of ethylene glycol are stirred for 5 hours at 120° C. and then for 12 hours at room temperature. 3000 ml of water are added, the mixture is filtered, the organic phase is dried over magnesium sulphate and the solvents are evaporated off under reduced pressure. The residue obtained is crystallized from cyclohexane; m.p.=132° C. the mixture is filtered the organic phase is dried over magnesium sulphate the solvents are evaporated off under reduced pressure The residue obtained is crystallized from cyclohexane

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

実験手順: The title compound was prepared from the reaction of 4-bromo-3,5-dichloroaniline (6.88 g, 28.6 mmol) and Copper(I)cyanide (2.56 g, 28.6 mmol) in DMF (48 mL) under microwave irradiation at 190° C. for 1 h. After the completion of the reaction, the mixture was cooled to RT and quenched with 200 mL of 12% ammonia solution. The resultant mixture was stirred for 30 min at RT and the precipitate was filtered, washed with water and dried under vacuum. Yield 3.725 g. 1H NMR (400 MHz; d6-DMSO): δ 6.70 (s, 1H), 6.79 (s, 1H). After the completion of the reaction quenched with 200 mL of 12% ammonia solution the precipitate was filtered washed with water dried under vacuum

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

実験手順: The title compound was prepared from the reaction of 4-bromo-3,5-dichloroaniline (6.88 g, 28.6 mmol) and Copper(I)cyanide (2.56 g, 28.6 mmol) in DMF (48 mL) under microwave irradiation at 190° C. for 1 h. After the completion of the reaction, the mixture was cooled to RT and quenched with 200 mL of 12% ammonia solution. The resultant mixture was stirred for 30 min at RT and the precipitate was filtered, washed with water and dried under vacuum. Yield 3.725 g. 1H NMR (400 MHz; d6-DMSO): δ 6.70 (s, 1H), 6.79 (s, 1H). After the completion of the reaction quenched with 200 mL of 12% ammonia solution the precipitate was filtered washed with water dried under vacuum

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

実験手順: 3,5-Dichloroaniline (10 g, 61.7 mmol) in acetonitrile (100 mL) was taken in a 3-necked flask fitted with a thermometer, condenser and a dropping funnel containing N-bromosuccinimide (10.99 g, 61.7 mmol) in acetonitrile (30 mL). N-bromosuccinimide solution was added slowly to the 3,5-dichloroaniline solution in the flask at 0° C. by maintaining the internal temperature below 5° C. After the addition of NBS, the reaction mixture was warmed to RT and stirred for further 3 h. After the completion of the reaction as evidenced by LC-MS, the mixture was diluted with 10% aq. NaHSO3 (150 mL). The solution was stirred for 15 min and evaporated to ⅓ of the total volume of the solvents. The resultant mixture was then diluted with water and extracted with ethyl acetate. The organic solvent was dried, evaporated and purified by CombiFlash to give pure 4-bromo-3,5-dichloroaniline. Yield 13.6 g. 1H NMR (400 MHz; d6-DMSO): δ 5.82 (bs, 2H), 6.75 (s, 2H). fitted with a thermometer, condenser and a dropping funnel by maintaining the internal temperature below 5° C After the completion of the reaction The solution was stirred for 15 min evaporated The resultant mixture was then diluted with water extracted with ethyl acetate The organic solvent was dried evaporated purified by CombiFlash

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

実験手順: The title compound was prepared as described in Example 159 substituting 4-bromo-3,5-dichloroaniline and (4-chlorophenyl)boronic acid for 4-bromo-3-chloroaniline and (4-(trifluoromethyl)phenyl)boronic acid, respectively.

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

実験手順: The title compound was prepared as described in Example 159 substituting 4-bromo-3,5-dichloroaniline and (4-chlorophenyl)boronic acid for 4-bromo-3-chloroaniline and (4-(trifluoromethyl)phenyl)boronic acid, respectively.

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 100 g of 4-bromo-3,5-dichlorophenylamine are added with stirring at 5° C. to a mixture of 125 ml of water and 90 ml of concentrated sulphuric acid. 230 g of crushed ice are added to the reaction mixture, followed by 29 g of sodium nitrite in 70 ml of water, and the reaction mixture is left stirring for 15 minutes. The reaction mixture is added rapidly to a mixture composed of 280 ml of concentrated sulphuric acid and 200 ml of water raised to 160° C., and the reaction mixture is left stirring at 160° C. for 1 hour. The reaction mixture is poured onto a water/crushed ice mixture and extracted with dichloromethane. The organic phase is dried over magnesium sulphate and the solvents are evaporated off under reduced pressure. The residue obtained is purified by chromatography on a column of silica gel, eluting with a 4/6 (v/v) cyclohexane/dichloromethane mixture. the reaction mixture is left The reaction mixture is added rapidly to a mixture the reaction mixture is left stirring at 160° C. for 1 hour crushed ice mixture extracted with dichloromethane The organic phase is dried over magnesium sulphate the solvents are evaporated off under reduced pressure The residue obtained is purified by chromatography on a column of silica gel eluting with a 4/6 (v/v) cyclohexane/dichloromethane mixture

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

実験手順: 202 g of N-(4-bromo-3,5-dichlorophenyl)acetamide and 220 g of sodium hydroxide (as an aqueous 50% solution) in 670 ml of ethylene glycol are stirred for 5 hours at 120° C. and then for 12 hours at room temperature. 3000 ml of water are added, the mixture is filtered, the organic phase is dried over magnesium sulphate and the solvents are evaporated off under reduced pressure. The residue obtained is crystallized from cyclohexane; m.p.=132° C. the mixture is filtered the organic phase is dried over magnesium sulphate the solvents are evaporated off under reduced pressure The residue obtained is crystallized from cyclohexane

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

実験手順: The title compound was prepared from the reaction of 4-bromo-3,5-dichloroaniline (6.88 g, 28.6 mmol) and Copper(I)cyanide (2.56 g, 28.6 mmol) in DMF (48 mL) under microwave irradiation at 190° C. for 1 h. After the completion of the reaction, the mixture was cooled to RT and quenched with 200 mL of 12% ammonia solution. The resultant mixture was stirred for 30 min at RT and the precipitate was filtered, washed with water and dried under vacuum. Yield 3.725 g. 1H NMR (400 MHz; d6-DMSO): δ 6.70 (s, 1H), 6.79 (s, 1H). After the completion of the reaction quenched with 200 mL of 12% ammonia solution the precipitate was filtered washed with water dried under vacuum

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

実験手順: 3,5-Dichloroaniline (10 g, 61.7 mmol) in acetonitrile (100 mL) was taken in a 3-necked flask fitted with a thermometer, condenser and a dropping funnel containing N-bromosuccinimide (10.99 g, 61.7 mmol) in acetonitrile (30 mL). N-bromosuccinimide solution was added slowly to the 3,5-dichloroaniline solution in the flask at 0° C. by maintaining the internal temperature below 5° C. After the addition of NBS, the reaction mixture was warmed to RT and stirred for further 3 h. After the completion of the reaction as evidenced by LC-MS, the mixture was diluted with 10% aq. NaHSO3 (150 mL). The solution was stirred for 15 min and evaporated to ⅓ of the total volume of the solvents. The resultant mixture was then diluted with water and extracted with ethyl acetate. The organic solvent was dried, evaporated and purified by CombiFlash to give pure 4-bromo-3,5-dichloroaniline. Yield 13.6 g. 1H NMR (400 MHz; d6-DMSO): δ 5.82 (bs, 2H), 6.75 (s, 2H). fitted with a thermometer, condenser and a dropping funnel by maintaining the internal temperature below 5° C After the completion of the reaction The solution was stirred for 15 min evaporated The resultant mixture was then diluted with water extracted with ethyl acetate The organic solvent was dried evaporated purified by CombiFlash