2,4-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:0.00; pressure:0.00; stir:

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of copper(I) cyanide (2.32 g, 25.9 mmol) in anhydrous dimethylsulfoxide (50 mL) is stirred at 60° C., and to this solution is added tert-butylnitrite (7.1 mL, 59.7 mmol) all at once. A solution of 2,4-dibromoaniline (5.0 g, 19.9 mmol) in anhydrous dimethylsulfoxide (30 mL) is added dropwise, via cannula, to the mixture. After the addition is complete the reaction mixture is stirred for 1 hr, cooled to 45° C., and then treated slowly with 5N HCl (50 mL). Five minutes later, the reaction mixture is cooled to ambient temperature and extracted with 1:1 ethyl acetate:hexane (2×300 mL). The combined organic layers are washed with water (100 mL) and saturated aqueous sodium chloride (100 mL), dried, concentrated under reduced pressure and the residue subjected to silica gel chromatography, eluting with hexane containing from 0–5% ethyl acetate. Fractions containing product are combined and concentrated under reduced pressure to provide the title compound (1.61 g, 31% yield). After the addition Five minutes later, the reaction mixture is cooled to ambient temperature extracted with 1:1 ethyl acetate The combined organic layers are washed with water (100 mL) and saturated aqueous sodium chloride (100 mL) dried concentrated under reduced pressure eluting with hexane containing from 0–5% ethyl acetate Fractions containing product concentrated under reduced pressure

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred, cooled (-5° C.) solution of 2,4-dibromoaniline (50.0 g,0.2 mol.) in concentrated HCl solution (110 mL) was added sodium nitrite (13.8 g, 0.2 mol.) in water (110 mL) dropwise at such a rate as to maintain temperature below 5° C. After complete addition, the mixture was further stirred at 5° C. for 30 minutes. A solution of tin chloride monohydrate (135.4 g, 0.6 mol.) in concentrated HCl (total volume 170 mL) was added dropwise again maintaining temperature below 5° C. After complete addition and 30 minutes of further stirring, the mixture was placed in the freezer overnight. The light brown solid which precipitated was isolated by filtration and washed with cold brine followed by a solution of petroleum ether/diethyl ether (2/1 by volume). This solid was slowly added to an ice cooled mixture of 50% sodium hydroxide solution/ethyl acetate. The mixture was extracted with ethyl acetate and the organic phase dried over magnesium sulfate. After filtration, the solution was concentrated to 400 mL total volume , diluted with diethyl ether (1.5 L) and treated with dry HCl. The product, 2,4-dibromophenyl-hydrazine hydrochloride (45.9 g) was isolated as a white solid and used without further purification. ##STR24## to maintain temperature below 5° C After complete addition maintaining temperature below 5° C After complete addition and 30 minutes of further stirring was placed in the freezer overnight The light brown solid which precipitated was isolated by filtration washed with cold brine This solid was slowly added to an ice cooled mixture of 50% sodium hydroxide solution/ethyl acetate The mixture was extracted with ethyl acetate the organic phase dried over magnesium sulfate After filtration the solution was concentrated to 400 mL total volume diluted with diethyl ether (1.5 L) treated with dry HCl

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

Procedure: 2,4-Dibromoaniline (500 mg), toluene (8 mL), and sodium hydride (60% in oil, 398 mg) were stirred for 10 minutes at room temperature and then 3,5-dichloro-1-(1-ethylpropyl)-2(1H)-pyrazinone (468 mg, Example 1, part B) was added. The reaction was heated at reflux 3 hours, cooled, and quenched with water (50 mL). The mixture was extracted with ethyl acetate (100 mL), which was washed with brine, then dried and concentrated. The crude product was chromatographed on silica gel using ethyl acetate/hexane (1:19) affording 400 mg of material, which was crystallized from ether/hexane to give the title compound (240 mg). Elemental analysis: calcd. for C15H16N3OClBr2: C, 40.07; H, 3.597; N, 9.356; Cl, 7.895; Br, 35.55. Found: C, 40.41; H, 3.49; N, 9.34; Cl, 8.27; Br, 35.71. The reaction was heated at reflux 3 hours cooled quenched with water (50 mL) The mixture was extracted with ethyl acetate (100 mL), which was washed with brine dried concentrated The crude product was chromatographed on silica gel

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: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 2,4-dibromoaniline to yield 2-[(2,4-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 2,4-dibromoaniline to yield 2-[(2,4-dibromophenyl)amino]phenylacetic acid.