2,5-dibromoaniline

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

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

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

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred mixture of 2.50 g (9.96 mmol) 2,5-dibromoaniline in 7 mL conc. sulfuric acid and 20 mL water, was added a solution of 1.00 g (14.5 mmol) sodium nitrite in 10 mL water dropwise at 0° C. and the mixture was stirred at this temperature for 1.25 h. A solution of 2.15 g (13.0 mmol) potassium iodide in 20 mL water was added dropwise under ice cooling. The ice bath was removed and the reaction mixture was heated to 65° C. for 30 min. After cooling to RT, the mixture was worked up by adding aqueous sodium thiosulfate solution, followed by extraction with PE/EtOAc. The combined organic phases were washed with aqueous sodium thiosulfate solution and saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (PE/EtOAc=100→96/4). The ice bath was removed After cooling to RT by adding aqueous sodium thiosulfate solution followed by extraction with PE/EtOAc The combined organic phases were washed with aqueous sodium thiosulfate solution and saturated aqueous sodium bicarbonate solution dried over sodium sulfate filtered concentrated in vacuo The crude material was purified by flash chromatography (PE/EtOAc=100→96/4)

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

Procedure: In the manner described in example 3, 2-bromophenylacetic acid is condensed with 2,5-dibromoaniline to yield 2-[(2,5-dibromophenyl)amino]phenylacetic acid.

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

Procedure: In the manner described in example 3, 2-bromophenylacetic acid is condensed with 2,5-dibromoaniline to yield 2-[(2,5-dibromophenyl)amino]phenylacetic acid.

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

Procedure: 2,5-Dibromoaniline 10 g was dispersed in diluted hydrochloric acid (concentrated hydrochloric acid 40 ml+water 30 ml), and an aqueous solution of NaNO2 3 g was dropwise added thereto at 0° C. The reaction solution was stirred for 40 minutes and then dropwise added at room temperature to an aqueous solution of potassium iodide 60 g which was separately prepared. After stirring at room temperature for 2 hours, methylene chloride and a small amount of sodium hydrogensulfite were added thereto, and the organic layer was extracted. The organic layer was washed with a 10% sodium hydrogensulfite aqueous solution and saturated brine and dried on anhydrous sodium sulfate, and then the solvent was distilled off. The product was refined by silica gel chromatography, whereby targeted 2,5-dibromoiodobenzene 10.5 g (yield: 73%) was obtained in the form of white crystal. at 0° C was separately prepared After stirring at room temperature for 2 hours the organic layer was extracted The organic layer was washed with a 10% sodium hydrogensulfite aqueous solution and saturated brine dried on anhydrous sodium sulfate the solvent was distilled off

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

Procedure: 2,5-Dibromoaniline 10 g was dispersed in diluted hydrochloric acid (concentrated hydrochloric acid 40 ml+water 30 ml), and an aqueous solution of NaNO2 3 g was dropwise added thereto at 0° C. The reaction solution was stirred for 40 minutes and then dropwise added at room temperature to an aqueous solution of potassium iodide 60 g which was separately prepared. After stirring at room temperature for 2 hours, methylene chloride and a small amount of sodium hydrogensulfite were added thereto, and the organic layer was extracted. The organic layer was washed with a 10% sodium hydrogensulfite aqueous solution and saturated brine and dried on anhydrous sodium sulfate, and then the solvent was distilled off. The product was refined by silica gel chromatography, whereby targeted 2,5-dibromoiodobenzene 10.5 g (yield: 73%) was obtained in the form of white crystal. at 0° C was separately prepared After stirring at room temperature for 2 hours the organic layer was extracted The organic layer was washed with a 10% sodium hydrogensulfite aqueous solution and saturated brine dried on anhydrous sodium sulfate the solvent was distilled off

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

Procedure: 2-Fluoro-4-(methylsulfonyl)benzoic acid (1 g, 4.6 mmol) dissolved in DCM (15 ml), cooled to 0° C. and added oxalyl chloride (0.6 ml, 6.9 mmol). Catalytic amount of DMF was added to this mixture and stirred at rt for 30 mins. After 30 mins, DCM removed on rotavapour and co-distilled the residue two times with DCM to obtain 2-fluoro-4-(methylsulfonyl)benzoyl chloride quantitatively. 2,5-Dibromoaniline (0.9 g, 3.59 mmol) dissolved in DCM (10 ml) and added Pyridine (0.34 g, 4.30 mmol) under nitrogen atmosphere. This mixture stirred at rt for 30 mins and added 2-fluoro-4-(methylsulfonyl)benzoyl chloride (1.01 g, 3.59 mmol). After continuing stirring at rt for 15 mins, reaction mass diluted with water and extracted with DCM. DCM layer washed with aq. NaHCO3 and DCM removed on rotavapour to obtain the solid. Solid was triturated with Et2O and Petether mixture (4:1) to obtain the titled compound (1.6 g) as a brown solid. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): 10.34 (s, 1H), 8.34-7.99 (m, 1H), 7.98-7.93 (m, 2H), 7.92-7.89 (m, 1H), 7.68 (d, J 8.6, 1H), 7.43 (dd, J 2.4, 8.6, 1H), 3.33 (s, 3H). After continuing stirring at rt for 15 mins reaction mass extracted with DCM DCM layer washed with aq. NaHCO3 and DCM removed on rotavapour to obtain the solid Solid was triturated with Et2O and Petether mixture (4:1)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred mixture of 2.50 g (9.96 mmol) 2,5-dibromoaniline in 7 mL conc. sulfuric acid and 20 mL water, was added a solution of 1.00 g (14.5 mmol) sodium nitrite in 10 mL water dropwise at 0° C. and the mixture was stirred at this temperature for 1.25 h. A solution of 2.15 g (13.0 mmol) potassium iodide in 20 mL water was added dropwise under ice cooling. The ice bath was removed and the reaction mixture was heated to 65° C. for 30 min. After cooling to RT, the mixture was worked up by adding aqueous sodium thiosulfate solution, followed by extraction with PE/EtOAc. The combined organic phases were washed with aqueous sodium thiosulfate solution and saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (PE/EtOAc=100→96/4). The ice bath was removed After cooling to RT by adding aqueous sodium thiosulfate solution followed by extraction with PE/EtOAc The combined organic phases were washed with aqueous sodium thiosulfate solution and saturated aqueous sodium bicarbonate solution dried over sodium sulfate filtered concentrated in vacuo The crude material was purified by flash chromatography (PE/EtOAc=100→96/4)

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

Procedure: In the manner described in example 3, 2-bromophenylacetic acid is condensed with 2,5-dibromoaniline to yield 2-[(2,5-dibromophenyl)amino]phenylacetic acid.

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