(4-chloro-2-fluorophenyl)hydrazine;hydrochloride

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

Procedure: Six parts of 4-chloro-2-fluorophenyl hydrazine hydrochloride was shaken with 100 parts of methylene chloride and 100 parts of 1-molar aqueous sodium hydroxide for one to two minutes until a clear two-phase solution was obtained. The organic phase was washed three times with 60 parts of water, dried with anhydrous magnesium sulfate, and evaporated under a reduced pressure of 50 to 300 mm Hg. to give 3.8 parts of pale tan 4-chloro-2-fluorophenyl hydrazine, m.p. 57°-63° C. was obtained The organic phase was washed three times with 60 parts of water dried with anhydrous magnesium sulfate evaporated under a reduced pressure of 50 to 300 mm Hg

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

Procedure: Six parts of 4-chloro-2-fluorophenyl hydrazine hydrochloride was shaken with 100 parts of methylene chloride and 100 parts of 1-molar aqueous sodium hydroxide for one to two minutes until a clear two-phase solution was obtained. The organic phase was washed three times with 60 parts of water, dried with anhydrous magnesium sulfate, and evaporated under a reduced pressure of 50 to 300 mm Hg. to give 3.8 parts of pale tan 4-chloro-2-fluorophenyl hydrazine, m.p. 57°-63° C. was obtained The organic phase was washed three times with 60 parts of water dried with anhydrous magnesium sulfate evaporated under a reduced pressure of 50 to 300 mm Hg

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

Procedure: By substituting 4-chlorophenylhydrazine hydrochloride in the above procedure for 4-chloro-2-fluorophenylhydrazine hydrochloride, 2-(4-chlorophenyl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-one was prepared, m.p. 183.5°-185° (Lit 186°-187°, Chem. Abs., 67, 11452h). was prepared

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

Procedure: By substituting 4-chlorophenylhydrazine hydrochloride in the above procedure for 4-chloro-2-fluorophenylhydrazine hydrochloride, 2-(4-chlorophenyl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-one was prepared, m.p. 183.5°-185° (Lit 186°-187°, Chem. Abs., 67, 11452h). was prepared

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

Procedure: By substituting 4-chlorophenylhydrazine hydrochloride in the above procedure for 4-chloro-2-fluorophenylhydrazine hydrochloride, 2-(4-chlorophenyl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-one was prepared, m.p. 183.5°-185° (Lit 186°-187°, Chem. Abs., 67 1145h). was prepared

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

Procedure: By substituting 4-chlorophenylhydrazine hydrochloride in the above procedure for 4-chloro-2fluorophenylhydrazine hydrochloride, 2-(4-chlorophenyl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-one was prepared, m.p. 183.5°-185° (Lit 186°-187°, Chem. Abs., 67, 11452h). was prepared

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

Procedure: 4-Chloro-2-fluorophenyl hydrazine hydrochloride (1 equiv.) is taken in 7% sulfuric acid in 1,4-dioxan. N-Methylpiperidine-4-one (0.76-1.4 equiv.) is added and the contents are stirred at RT for 10 min. The reaction mixture is then stirred at 100° C. for 6 h. The reaction is monitored by TLC and LCMS. After completion of the reaction, the reaction mixture is concentrated and then slowly quenched with aq. NaHCO3 solution, followed by extraction with EtOAc. The organic layer is dried over anhydrous sodium sulfate and evaporated to dryness. The crude product is purified by column chromatography to afford 8-chloro-6-fluoro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole. The reaction mixture is then stirred at 100° C. for 6 h After completion of the reaction the reaction mixture is concentrated slowly quenched with aq. NaHCO3 solution followed by extraction with EtOAc The organic layer is dried over anhydrous sodium sulfate evaporated to dryness The crude product is purified by column chromatography

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

Procedure: 4-Chloro-2-fluorophenyl hydrazine hydrochloride (1 equiv.) is taken in 7% sulfuric acid in 1,4-dioxan. N-Methylpiperidine-4-one (0.76-1.4 equiv.) is added and the contents are stirred at RT for 10 min. The reaction mixture is then stirred at 100° C. for 6 h. The reaction is monitored by TLC and LCMS. After completion of the reaction, the reaction mixture is concentrated and then slowly quenched with aq. NaHCO3 solution, followed by extraction with EtOAc. The organic layer is dried over anhydrous sodium sulfate and evaporated to dryness. The crude product is purified by column chromatography to afford 8-chloro-6-fluoro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole. The reaction mixture is then stirred at 100° C. for 6 h After completion of the reaction the reaction mixture is concentrated slowly quenched with aq. NaHCO3 solution followed by extraction with EtOAc The organic layer is dried over anhydrous sodium sulfate evaporated to dryness The crude product is purified by column chromatography

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

Procedure: The pH of the 4-chloro-2-fluorophenylhydrazine hydrochloride slurry was adjusted to 3.8-4.0 and the temperature was raised to 90°-95°. To this mixture was added an aqueous solution (preheated to 90°-95°) of 1118 parts of cyclohexanone-2-carboxamide prepared as previously described. The resulting mixture was heated for 1-2 hr at 90°-95° during which time the product precipitated from solution. The product was isolated by filtration, washed by digestion with toluene and air-dried to give 1771 parts of an indazolone, an off-white solid mp 179-182 which was 2-(4-chloro-2-fluorophenyl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-one. the temperature was raised to 90°-95° prepared The resulting mixture was heated for 1-2 hr at 90°-95° during which time the product precipitated from solution The product was isolated by filtration washed by digestion with toluene air-dried

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

Procedure: By substituting 4-chlorophenylhydrazine hydrochloride in the above procedure for 4-chloro-2-fluorophenylhydrazine hydrochloride, 2-(4-chlorophenyl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-one was prepared, m.p. 183.5°-185° (Lit 186°-187°, Chem. Abs., 67, 11452h). was prepared

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

Procedure: Six parts of 4-chloro-2-fluorophenyl hydrazine hydrochloride was shaken with 100 parts of methylene chloride and 100 parts of 1-molar aqueous sodium hydroxide for one to two minutes until a clear two-phase solution was obtained. The organic phase was washed three times with 60 parts of water, dried with anhydrous magnesium sulfate, and evaporated under a reduced pressure of 50 to 300 mm Hg. to give 3.8 parts of pale tan 4-chloro-2-fluorophenyl hydrazine, m.p. 57°-63° C. was obtained The organic phase was washed three times with 60 parts of water dried with anhydrous magnesium sulfate evaporated under a reduced pressure of 50 to 300 mm Hg