(4-bromophenyl)hydrazine;hydrochloride

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

Procedure: p-Bromophenylhydrazine hydrochloride (10 mmol, 2.5 g) was added to 2-acetyl-3-oxo-butyric acid ethyl ester (10 mmol, 1.7 g) in ethanol (10 mL) and pyridine (10 mL). The mixture was stirred overnight at room temperature. Thin layer chromatographic (TLC) analysis using chloroform indicated the reaction was complete. The solvents were removed under vacuum. The residue was dissolved in 150 mL ether, then washed with 50 mL water to remove the pyridine. The ether, was dried over sodium sulfate (NaSO4), the solids filtered, then the solvents were removed under vacuum. The resulting oil was purified on a silica column. The named product crystallized upon standing in the column effluent, m.p. 71° C.-73° C. Analysis by 1H-NMR and 13C-NMR verified synthesis the named product. The solvents were removed under vacuum The residue was dissolved in 150 mL ether washed with 50 mL water to remove the pyridine The ether, was dried over sodium sulfate (NaSO4) the solids filtered the solvents were removed under vacuum The resulting oil was purified on a silica column The named product crystallized synthesis the named product

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

Procedure: Following a published procedure (Gundersen, E. G. U.S. Patent App. Publ. US 2005/070592) 2-Butanone (0.11 mL, 1.278 mmol) was added to a solution of 4-bromophenylhydrazine hydrochloride (0.300 g, 1.342 mmol in EtOH (3.8 mL). The mixture was heated to reflux for 22 h, concentrated in vacuo, and partitioned between EtOAc and 1N HCl. The organic layer was washed with H2O and saturated aqueous NaHCO3, dried over Na2SO4, filtered, and concentrated. The crude residue was purified by chromatography (SiO2, 0-20% EtOAc/Hexane) to afford the desired indole as a pink powder (200 mg, 67%). The mixture was heated to reflux for 22 h concentrated in vacuo partitioned between EtOAc and 1N HCl The organic layer was washed with H2O and saturated aqueous NaHCO3 dried over Na2SO4 filtered concentrated The crude residue was purified by chromatography (SiO2, 0-20% EtOAc/Hexane)

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

Procedure: Cyclohexanone (1.16 mL, 11.2 mmol) and 4-bromo-phenylhydrazine hydrochloride (2.50 g, 11.2 mmol) were refluxed in cyclohexanone (18 mL) and acetic acid (AcOH) (12 L) for 24 h. The reaction mixture was treated with saturated sodium bicarbonate (Na2CO3) and extracted with ethyl acetate, dried (Na2CO3) and concentrated. The product was purified by column chromatography, giving 479 mg of compound 30 as a solid. extracted with ethyl acetate dried (Na2CO3) concentrated The product was purified by column chromatography

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

Procedure: Reaction of 4-bromophenylhydrazine hydrochloride (4.0g, 18.1 mmol) with 4-phthalimido-cyclohexanone (4.39g, 18.1 mmol) in refluxing n-butanol for 20 min, followed by cooling, filtration, and evaporation of the filtrate to dryness yielded 3-phthalimido-6-bromo-1,2,3,4-tetrahydrocarbazole as an orange solid (7.45g). by cooling filtration, and evaporation of the filtrate to dryness

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1.91 g (8.55.10−3 mol) of 4-bromophenylhydrazine hydrochloride and 0.73 g (8.9.10−3 mol) of sodium acetate in 17 ml of water is prepared and 2.05 ml (35.8.10−3 mol) of acetic acid are added. This mixture is subsequently heated to 70° C., with stirring, and a suspension of 2.0 g (8.54.10−3 mol) of ethyl ε-oxobenzenehexanoate in 27 ml of water is then added slowly. The reaction mixture is stirred at 70-80° C. for 45 min and then at room temperature for 12 hours, after which it is extracted with 2 times 50 ml of ethyl acetate. The organic phase is washed with water, dried over magnesium sulfate and concentrated under reduced pressure to give 3.38 g of the expected compound, which is used directly in the next step. is prepared is then added slowly The reaction mixture is stirred at 70-80° C. for 45 min after which it is extracted with 2 times 50 ml of ethyl acetate The organic phase is washed with water dried over magnesium sulfate concentrated under reduced pressure

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

Procedure: A mixture of 4-bromophenylhydrazine hydrochloride (5.g, 22.4 mmol) and urea (8.1 g, 134 mmol) was heated to 80° C. overnight in 1-methyl-2-pyrrolidinone (25 mL). The reaction was poured into water (250 mL) and concentrated ammonia was added until basic pH. The solution was cooled on an ice bath and the semicarbazone filtered off. The semicarbazone (1.0 g, 4,4 mmol) was stirred in triethyl orthoformiate (B mL) at 90° C. for three days. The reaction mixture was cooled to room temperature and the crude material filtered off. Re-crystallisation from methanol afforded the desired product. was added until basic pH The solution was cooled on an ice bath the semicarbazone filtered off the crude material filtered off

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

Procedure: A mixture of 3-pyridin-propionaldehyde (1 g; 0.0074 mol) and of 4-bromophenylhydrazin hydrochloride (1.8 g; 0.0074 mol) with acetic acid (4.44 ml) in absolute ethanol (50 ml) was refluxed for 3 hours. The reaction was then quenched with a saturated solution of aqueous sodium carbonate and the product was extracted with ethyl acetate. The organic extract was dried (MGSO4) and evaporated under vacuum. After purification by Flash Chromatography on silica gel using as eluent methylene chloride/methanol (98/2), the desired compound was obtained. The reaction was then quenched with a saturated solution of aqueous sodium carbonate the product was extracted with ethyl acetate The organic extract was dried (MGSO4) evaporated under vacuum After purification by Flash Chromatography on silica gel using as eluent methylene chloride/methanol (98/2)

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

Procedure: Following a published procedure (Gundersen, E. G. U.S. Patent App. Publ. US 2005/070592) 2-Butanone (0.11 mL, 1.278 mmol) was added to a solution of 4-bromophenylhydrazine hydrochloride (0.300 g, 1.342 mmol in EtOH (3.8 mL). The mixture was heated to reflux for 22 h, concentrated in vacuo, and partitioned between EtOAc and 1N HCl. The organic layer was washed with H2O and saturated aqueous NaHCO3, dried over Na2SO4, filtered, and concentrated. The crude residue was purified by chromatography (SiO2, 0-20% EtOAc/Hexane) to afford the desired indole as a pink powder (200 mg, 67%). The mixture was heated to reflux for 22 h concentrated in vacuo partitioned between EtOAc and 1N HCl The organic layer was washed with H2O and saturated aqueous NaHCO3 dried over Na2SO4 filtered concentrated The crude residue was purified by chromatography (SiO2, 0-20% EtOAc/Hexane)

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

Procedure: A mixture consisting of 44.7 g. (0.20 mole) p-bromophenylhydrazine hydrochloride, 250 ml. diethyl ether, 70 ml. (0.504 mole) triethylamine, and 35.0 g. (0.20 mole) p-chlorobenzoyl chloride in 50 ml. diethyl ether (mixed in that order at -5° to -15° C. during 20 minutes) was stirred continuously for about 16 hrs. at about 25° C. The reaction mixture was filtered, and the solids on the filter were washed with water and then recrystallized from 95% ethanol. There was thus obtained 15.5 g. p-chlorobenzoic acid (p-bromophenyl)hydrazide having a melting point of 185° C. (dec.). An analytical sample melting at 184.5° C. (dec.) was obtained after two recrystallizations from ethyl acetate. at about 25° C The reaction mixture was filtered the solids on the filter were washed with water recrystallized from 95% ethanol An analytical sample melting at 184.5° C. (dec.) was obtained after two recrystallizations from ethyl acetate

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

Procedure: To a mixture of 6.0 gm (42.0 mMol) 4-dimethylaminocyclohexanone and 9.5 gm (42.0 mMol) 4-bromophenyl-hydrazine hydrochloride in 100 mL ethanol were added 3.4 mL (42 mMol) pyridine. The resultant mixture was then heated at reflux for 2 hours and then stirred at ambient temperature for 18 hours. The reaction mixture was then treated with aqueous potassium carbonate and extracted well with dichloromethane. The organic phases were combined, dried over sodium sulfate and concentrated under reduced pressure. The resultant residue was treated with toluene and concentrated again under reduced pressure to give 11.3 gm (87%) of the desired compound. at reflux for 2 hours extracted well with dichloromethane dried over sodium sulfate concentrated under reduced pressure The resultant residue was treated with toluene concentrated again under reduced pressure

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

Procedure: To a stirred suspension of dimethyl-7-chloro-4-hydroxyquinoline-2,3-dicarboxylate (1.90 g, 6.40 mM) and 4-bromophenylhydrazine hydrochloride (10.0 g, 44.7 mM) in ethanol (35 mL) was added triethylamine (7.1 mL, 51.1 mM). The resulting brown solution was refluxed for 22 hours during which time a tan precipitate formed. This mixture was cooled to room temperature and filtered to give the 4-bromophenylhydrazine salt of the title compound as a white powder (1.69 g). This material was refluxed in glacial acetic acid (20 mL) for 3 hours and cooled to room temperature. The resulting tan suspension was filtered and the solids washed with glacial acetic acid and then ether to give the title compound (1.15 g, 43%) as a tan powder, mp 393-394° C.; MS(CI): 420 (M+H). The resulting brown solution was refluxed for 22 hours during which time a tan precipitate formed filtered

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

Procedure: 1-(4-bromophenyl)-4-phenylazo-1H-pyrazole-3,5-diamine was prepared using 85 mg (0.5 mmol) of 2-(phenylhydrazono)malononitrile, which was derived from aniline (10 mL, 107 mmol) and malononitrile (161 mmol), and 4-bromophenylhydrazine hydrochloride (112 mg, 0.5 mmol) with the addition of 0.5 mL of 5% sodium hydroxide solution. Solids had not formed after heating the reaction at 75° C. for 3 hrs, however, analysis of the reaction solution by TLC indicated that no starting material remained. The solution was allowed to cool to ambient temperature and the solvent was evaporated. The residue was dissolved in methanol and then precipitated by the addition of water. The resulting solid was isolated by filtration and dried to yield 49 mg (27%) of the compound as a brown solid. Solids had not formed after heating the reaction at 75° C. for 3 hrs the solvent was evaporated The residue was dissolved in methanol precipitated by the addition of water The resulting solid was isolated by filtration dried