(3,5-dichlorophenyl)hydrazine;hydrochloride

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

Procedure: To 30 ml of acetic acid were added 1.54 g of N-benzyl-4-oxocyclohexane-1,2-dicarboximide, 3.0 g of zinc chloride and 1.54 g of 3,5-dichlorophenylhydrazine hydrochloride. The mixture was refluxed for 2 hours. Acetic acid was removed by distillation under reduced pressure. To the residue were added 150 ml of ethyl acetate and 50 ml of water. The organic layer was separated, washed with diluted hydrochloric acid, an aqueous saturated sodium chloride solution, an aqueous saturated sodium hydrogencarbonate solution and an aqueous saturated sodium chloride solution in this order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography (eluant: toluene/ethyl acetate=30/1 to 20/1) to obtain 670 mg (yield: 28%) of N-benzyl-5,7-dichloro-1,2,3,4-tetrahydrocarbazole-3,4-dicarboximide [IR (KBr) cm-1 : 3320, 1770, 1695] and 400 mg (yield: 17%) of N-benzyl-5,7-dichloro-1,2,3,4-tetrahydrocarbazole-2,3-dicarboximide [IR (KBr) cm-1 : 3310, 1765, 1690], both as colorless crystals. The mixture was refluxed for 2 hours Acetic acid was removed by distillation under reduced pressure To the residue were added 150 ml of ethyl acetate and 50 ml of water The organic layer was separated washed with diluted hydrochloric acid an aqueous saturated sodium chloride solution, an aqueous saturated sodium hydrogencarbonate solution and an aqueous saturated sodium chloride solution in this order, and dried over anhydrous magnesium sulfate The solvent was removed by distillation under reduced pressure The residue was purified by column chromatography (eluant: toluene/ethyl acetate=30/1 to 20/1)

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

Procedure: A mixture of 3,5-dichlorophenylhydrazine hydrochloride (5.07 g) and ethyl pyruvate (3.96 ml) in ethyl alcohol (30 ml) was refluxed for 2 hours, and the solvent was evaporated under reduced pressure. The residual solid was triturated with hexane to give ethyl 2-(3,5-dichlorophenylhydrazino)propionate (5.60 g). APCI-Mass m/Z 275/277 (M+H). was refluxed for 2 hours the solvent was evaporated under reduced pressure The residual solid was triturated with hexane

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

Procedure: A mixture of 3,5-dichlorophenylhydrazine hydrochloride (5.07 g) and ethyl pyruvate (3.96 ml) in ethyl alcohol (30 ml) was refluxed for 2 hours, and the solvent was evaporated under reduced pressure. The residual solid was triturated with hexane to give ethyl 2-(3,5-dichlorophenylhydrazino)propionate (5.60 g). APCI-Mass m/Z 275/277 (M+H). was refluxed for 2 hours the solvent was evaporated under reduced pressure The residual solid was triturated with hexane

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

Procedure: To 30 ml of acetic acid were added 1.54 g of N-benzyl-4-oxocyclohexane-1,2-dicarboximide, 3.0 g of zinc chloride and 1.54 g of 3,5-dichlorophenylhydrazine hydrochloride. The mixture was refluxed for 2 hours. Acetic acid was removed by distillation under reduced pressure. To the residue were added 150 ml of ethyl acetate and 50 ml of water. The organic layer was separated, washed with diluted hydrochloric acid, an aqueous saturated sodium chloride solution, an aqueous saturated sodium hydrogencarbonate solution and an aqueous saturated sodium chloride solution in this order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography (eluant: toluene/ethyl acetate=30/1 to 20/1) to obtain 670 mg (yield: 28%) of N-benzyl-5,7-dichloro-1,2,3,4-tetrahydrocarbazole-3,4-dicarboximide [IR (KBr) cm-1 : 3320, 1770, 1695] and 400 mg (yield: 17%) of N-benzyl-5,7-dichloro-1,2,3,4-tetrahydrocarbazole-2,3-dicarboximide [IR (KBr) cm-1 : 3310, 1765, 1690], both as colorless crystals. The mixture was refluxed for 2 hours Acetic acid was removed by distillation under reduced pressure To the residue were added 150 ml of ethyl acetate and 50 ml of water The organic layer was separated washed with diluted hydrochloric acid an aqueous saturated sodium chloride solution, an aqueous saturated sodium hydrogencarbonate solution and an aqueous saturated sodium chloride solution in this order, and dried over anhydrous magnesium sulfate The solvent was removed by distillation under reduced pressure The residue was purified by column chromatography (eluant: toluene/ethyl acetate=30/1 to 20/1)

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

Procedure: To 30 ml of acetic acid were added 1.54 g of N-benzyl-4-oxocyclohexane-1,2-dicarboximide, 3.0 g of zinc chloride and 1.54 g of 3,5-dichlorophenylhydrazine hydrochloride. The mixture was refluxed for 2 hours. Acetic acid was removed by distillation under reduced pressure. To the residue were added 150 ml of ethyl acetate and 50 ml of water. The organic layer was separated, washed with diluted hydrochloric acid, an aqueous saturated sodium chloride solution, an aqueous saturated sodium hydrogencarbonate solution and an aqueous saturated sodium chloride solution in this order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography (eluant: toluene/ethyl acetate=30/1 to 20/1) to obtain 670 mg (yield: 28%) of N-benzyl-5,7-dichloro-1,2,3,4-tetrahydrocarbazole-3,4-dicarboximide [IR (KBr) cm-1 : 3320, 1770, 1695] and 400 mg (yield: 17%) of N-benzyl-5,7-dichloro-1,2,3,4-tetrahydrocarbazole-2,3-dicarboximide [IR (KBr) cm-1 : 3310, 1765, 1690], both as colorless crystals. The mixture was refluxed for 2 hours Acetic acid was removed by distillation under reduced pressure To the residue were added 150 ml of ethyl acetate and 50 ml of water The organic layer was separated washed with diluted hydrochloric acid an aqueous saturated sodium chloride solution, an aqueous saturated sodium hydrogencarbonate solution and an aqueous saturated sodium chloride solution in this order, and dried over anhydrous magnesium sulfate The solvent was removed by distillation under reduced pressure The residue was purified by column chromatography (eluant: toluene/ethyl acetate=30/1 to 20/1)

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

Procedure: Prepared according to general procedure A from 338.5 mg (1.92 mmol) 5H-pyrido[3,2-b]azepine-6,9(7H,8H)-dione, 452 mg (2.11 mmol) (3,5-dichlorophenyl)hydrazine hydrochloride, and 169 mg (2.11 mmol) sodium acetate. Recrystallization from ethanol afforded a beige powder. Yield: 213 mg (33%); m.p. 270° C. (dec.); IR (KBr): 3281 cm−1 (NH), 3067/3029 cm−1 (CH-arom.), 2892 cm−1 (CH-aliph.), 1671 cm−1 (C═O); 1H-NMR (DMSO-d6, 400 MHz): δ (ppm)=2.57-2.60 (m, 2H, azepine-CH2, part of AA′XX′-system), 3.02-3.05 (m, 2H, azepine-CH2, part of AA′XX′-system), 6.91-6.92 (m, 1H, arom. H), 7.16 (d, 2H, 1.9 Hz, arom. H), 7.37-7.44 (m, 2H, arom. H), 8.44 (dd, 1H, 4.2/1.8 Hz, arom. H), 9.72 (s, 1H, NH), 9.81 (s, 1H, NH); C15H12Cl2N4O (335.20). Prepared Recrystallization from ethanol afforded a beige powder

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

Procedure: Prepared according to general procedure A from 338.5 mg (1.92 mmol) 5H-pyrido[3,2-b]azepine-6,9(7H,8H)-dione, 452 mg (2.11 mmol) (3,5-dichlorophenyl)hydrazine hydrochloride, and 169 mg (2.11 mmol) sodium acetate. Recrystallization from ethanol afforded a beige powder. Yield: 213 mg (33%); m.p. 270° C. (dec.); IR (KBr): 3281 cm−1 (NH), 3067/3029 cm−1 (CH-arom.), 2892 cm−1 (CH-aliph.), 1671 cm−1 (C═O); 1H-NMR (DMSO-d6, 400 MHz): δ (ppm)=2.57-2.60 (m, 2H, azepine-CH2, part of AA′XX′-system), 3.02-3.05 (m, 2H, azepine-CH2, part of AA′XX′-system), 6.91-6.92 (m, 1H, arom. H), 7.16 (d, 2H, 1.9 Hz, arom. H), 7.37-7.44 (m, 2H, arom. H), 8.44 (dd, 1H, 4.2/1.8 Hz, arom. H), 9.72 (s, 1H, NH), 9.81 (s, 1H, NH); C15H12Cl2N4O (335.20). Prepared Recrystallization from ethanol afforded a beige powder

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

Procedure: A solution of ethyl benzoylacetate (0.192 g, 1.00 mmol), 3,5-dichlorophenylhydrazine hydrochloride (0.235 g, 1.10 mmol), and p-toluenesulfonic acid monohydrate (0.019 g, 0.10 mmol) in ethanol (10 mL) was heated at reflux for 24 hours. The reaction solution was concentrated and the resulting residue was partitioned between ethyl acetate and aqueous 1N hydrochloric acid solution. The organic layer was further washed with water and brine, dried (sodium sulfate) and concentrated to afford a yellow solid. The crude product was triturated with hexanes and collected by suction filtration. Air drying afforded 0.174 g (57%) of product as a bright yellow solid: 1H NMR (DMSO-d6) δ12.60-12.40 (br s, 1H), 7.92 (s, 2H), 7.87-7.83 (d, 2H), 7.50 (s, 1H), 7.44-7.38 (m, 2H), 7.36-7.31 (m, 1H), 6.02 (s, 1H) ppm. at reflux for 24 hours The reaction solution was concentrated the resulting residue was partitioned between ethyl acetate and aqueous 1N hydrochloric acid solution The organic layer was further washed with water and brine dried (sodium sulfate) concentrated to afford a yellow solid The crude product was triturated with hexanes collected by suction filtration Air drying

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

Procedure: Prepared from 3,5-dichlorophenylhydrazine hydrochloride in an analogous manner to that described for 6-chloro-3,3-dimethyl-2,3-dihydro-1H-indole (Preparation 25). MS: [M+H]+=216.

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

Procedure: A mixture of 3,5-dichlorophenylhydrazine hydrochloride (5.07 g) and ethyl pyruvate (3.96 ml) in ethyl alcohol (30 ml) was refluxed for 2 hours, and the solvent was evaporated under reduced pressure. The residual solid was triturated with hexane to give ethyl 2-(3,5-dichlorophenylhydrazino)propionate (5.60 g). APCI-Mass m/Z 275/277 (M+H). was refluxed for 2 hours the solvent was evaporated under reduced pressure The residual solid was triturated with hexane

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

Procedure: To 30 ml of acetic acid were added 1.54 g of N-benzyl-4-oxocyclohexane-1,2-dicarboximide, 3.0 g of zinc chloride and 1.54 g of 3,5-dichlorophenylhydrazine hydrochloride. The mixture was refluxed for 2 hours. Acetic acid was removed by distillation under reduced pressure. To the residue were added 150 ml of ethyl acetate and 50 ml of water. The organic layer was separated, washed with diluted hydrochloric acid, an aqueous saturated sodium chloride solution, an aqueous saturated sodium hydrogencarbonate solution and an aqueous saturated sodium chloride solution in this order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography (eluant: toluene/ethyl acetate=30/1 to 20/1) to obtain 670 mg (yield: 28%) of N-benzyl-5,7-dichloro-1,2,3,4-tetrahydrocarbazole-3,4-dicarboximide [IR (KBr) cm-1 : 3320, 1770, 1695] and 400 mg (yield: 17%) of N-benzyl-5,7-dichloro-1,2,3,4-tetrahydrocarbazole-2,3-dicarboximide [IR (KBr) cm-1 : 3310, 1765, 1690], both as colorless crystals. The mixture was refluxed for 2 hours Acetic acid was removed by distillation under reduced pressure To the residue were added 150 ml of ethyl acetate and 50 ml of water The organic layer was separated washed with diluted hydrochloric acid an aqueous saturated sodium chloride solution, an aqueous saturated sodium hydrogencarbonate solution and an aqueous saturated sodium chloride solution in this order, and dried over anhydrous magnesium sulfate The solvent was removed by distillation under reduced pressure The residue was purified by column chromatography (eluant: toluene/ethyl acetate=30/1 to 20/1)