(3-chloro-2-methylphenyl)hydrazine

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

Procedure: The title compound was prepared in accordance with the general method of example 25b) from a) (3-chloro-2-methyl-phenyl)-hydrazine and ethyl pyruvate.

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

Procedure: The title compound was prepared in accordance with the general method of example 25b) from a) (3-chloro-2-methyl-phenyl)-hydrazine and ethyl pyruvate.

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

Procedure: cis-2-Oxobicyclo[4.2.0]octane-1-acetic acid ethyl ester (3.7 g, 18.87 mmol) prepared by the process of Ziegler et al, J. Am. Chem. Soc., 104, 7181 (1982) and 3-chloro-2-methylphenylhydrazine (2.95 g, 18.87 mmol) were dissolved in 50 mL of toluene and refluxed under nitrogen with azeotropic removal of water for 48 hours. The toluene was removed and 13 mL of acetic acid and 2.78 mL (22.64 mmol) of borontrifluoride etherate was added to the residue. The reaction mixture was then allowed to reflux under nitrogen for 30 minutes. The reaction mixture was then poured into 50 mL of water and extracted with 4×30 mL of ether. The combined organic layers were washed with 4×30 mL of 1N HCl, 1×30 mL of 1N NaOH, and 1×30 mL of brine. The ether layers were dried over MgSO4 and concentrated in vacuo affording 5.7 g of crude product. Flash chromatography (70 mm column, 5% ethyl acetate/petroleum ether eluant) afforded 2.7 g (45%) of cis-7-chloro-1,2,2a,3,4,9-hexahydro-8-methyl-9bH-cyclobuta[a]carbazole-9b-acetic acid ethyl ester. The toluene was removed to reflux under nitrogen for 30 minutes extracted with 4×30 mL of ether The combined organic layers were washed with 4×30 mL of 1N HCl, 1×30 mL of 1N NaOH, and 1×30 mL of brine The ether layers were dried over MgSO4 concentrated in vacuo affording 5.7 g of crude product

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

Procedure: cis-2-Oxobicyclo[4.2.0]octane-1-acetic acid ethyl ester (3.7 g, 18.87 mmol) prepared by the process of Ziegler et al, J. Am. Chem. Soc., 104, 7181 (1982) and 3-chloro-2-methylphenylhydrazine (2.95 g, 18.87 mmol) were dissolved in 50 mL of toluene and refluxed under nitrogen with azeotropic removal of water for 48 hours. The toluene was removed and 13 mL of acetic acid and 2.78 mL (22.64 mmol) of borontrifluoride etherate was added to the residue. The reaction mixture was then allowed to reflux under nitrogen for 30 minutes. The reaction mixture was then poured into 50 mL of water and extracted with 4×30 mL of ether. The combined organic layers were washed with 4×30 mL of 1N HCl, 1×30 mL of 1N NaOH, and 1×30 mL of brine. The ether layers were dried over MgSO4 and concentrated in vacuo affording 5.7 g of crude product. Flash chromatography (70 mm column, 5% ethyl acetate/petroleum ether eluant) afforded 2.7 g (45%) of cis-7-chloro-1,2,2a,3,4,9-hexahydro-8-methyl-9bH-cyclobuta[a]carbazole-9b-acetic acid ethyl ester. The toluene was removed to reflux under nitrogen for 30 minutes extracted with 4×30 mL of ether The combined organic layers were washed with 4×30 mL of 1N HCl, 1×30 mL of 1N NaOH, and 1×30 mL of brine The ether layers were dried over MgSO4 concentrated in vacuo affording 5.7 g of crude product

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

Procedure: Reaction of 3-((E)-3-dimethylamino-acryloyl)-1-(3-trifluoromethoxy-phenyl)-1H-pyridazin-4-one (A-6) and (3-chloro-2-methyl-phenyl)-hydrazine according to example 43 gave the desired product. MS: M=447.3 (M+H)+

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

Procedure: The title compound was prepared in accordance with the general method of example 25b) from a) (3-chloro-2-methyl-phenyl)-hydrazine and ethyl pyruvate.

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

Procedure: cis-2-Oxobicyclo[4.2.0]octane-1-acetic acid ethyl ester (3.7 g, 18.87 mmol) prepared by the process of Ziegler et al, J. Am. Chem. Soc., 104, 7181 (1982) and 3-chloro-2-methylphenylhydrazine (2.95 g, 18.87 mmol) were dissolved in 50 mL of toluene and refluxed under nitrogen with azeotropic removal of water for 48 hours. The toluene was removed and 13 mL of acetic acid and 2.78 mL (22.64 mmol) of borontrifluoride etherate was added to the residue. The reaction mixture was then allowed to reflux under nitrogen for 30 minutes. The reaction mixture was then poured into 50 mL of water and extracted with 4×30 mL of ether. The combined organic layers were washed with 4×30 mL of 1N HCl, 1×30 mL of 1N NaOH, and 1×30 mL of brine. The ether layers were dried over MgSO4 and concentrated in vacuo affording 5.7 g of crude product. Flash chromatography (70 mm column, 5% ethyl acetate/petroleum ether eluant) afforded 2.7 g (45%) of cis-7-chloro-1,2,2a,3,4,9-hexahydro-8-methyl-9bH-cyclobuta[a]carbazole-9b-acetic acid ethyl ester. The toluene was removed to reflux under nitrogen for 30 minutes extracted with 4×30 mL of ether The combined organic layers were washed with 4×30 mL of 1N HCl, 1×30 mL of 1N NaOH, and 1×30 mL of brine The ether layers were dried over MgSO4 concentrated in vacuo affording 5.7 g of crude product

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

Procedure: cis-2-Oxobicyclo[4.2.0]octane-1-acetic acid ethyl ester (3.7 g, 18.87 mmol) prepared by the process of Ziegler et al, J. Am. Chem. Soc., 104, 7181 (1982) and 3-chloro-2-methylphenylhydrazine (2.95 g, 18.87 mmol) were dissolved in 50 mL of toluene and refluxed under nitrogen with azeotropic removal of water for 48 hours. The toluene was removed and 13 mL of acetic acid and 2.78 mL (22.64 mmol) of borontrifluoride etherate was added to the residue. The reaction mixture was then allowed to reflux under nitrogen for 30 minutes. The reaction mixture was then poured into 50 mL of water and extracted with 4×30 mL of ether. The combined organic layers were washed with 4×30 mL of 1N HCl, 1×30 mL of 1N NaOH, and 1×30 mL of brine. The ether layers were dried over MgSO4 and concentrated in vacuo affording 5.7 g of crude product. Flash chromatography (70 mm column, 5% ethyl acetate/petroleum ether eluant) afforded 2.7 g (45%) of cis-7-chloro-1,2,2a,3,4,9-hexahydro-8-methyl-9bH-cyclobuta[a]carbazole-9b-acetic acid ethyl ester. The toluene was removed to reflux under nitrogen for 30 minutes extracted with 4×30 mL of ether The combined organic layers were washed with 4×30 mL of 1N HCl, 1×30 mL of 1N NaOH, and 1×30 mL of brine The ether layers were dried over MgSO4 concentrated in vacuo affording 5.7 g of crude product

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

Procedure: cis-2-Oxobicyclo[4.2.0]octane-1-acetic acid ethyl ester (3.7 g, 18.87 mmol) prepared by the process of Ziegler et al, J. Am. Chem. Soc., 104, 7181 (1982) and 3-chloro-2-methylphenylhydrazine (2.95 g, 18.87 mmol) were dissolved in 50 mL of toluene and refluxed under nitrogen with azeotropic removal of water for 48 hours. The toluene was removed and 13 mL of acetic acid and 2.78 mL (22.64 mmol) of borontrifluoride etherate was added to the residue. The reaction mixture was then allowed to reflux under nitrogen for 30 minutes. The reaction mixture was then poured into 50 mL of water and extracted with 4×30 mL of ether. The combined organic layers were washed with 4×30 mL of 1N HCl, 1×30 mL of 1N NaOH, and 1×30 mL of brine. The ether layers were dried over MgSO4 and concentrated in vacuo affording 5.7 g of crude product. Flash chromatography (70 mm column, 5% ethyl acetate/petroleum ether eluant) afforded 2.7 g (45%) of cis-7-chloro-1,2,2a,3,4,9-hexahydro-8-methyl-9bH-cyclobuta[a]carbazole-9b-acetic acid ethyl ester. The toluene was removed to reflux under nitrogen for 30 minutes extracted with 4×30 mL of ether The combined organic layers were washed with 4×30 mL of 1N HCl, 1×30 mL of 1N NaOH, and 1×30 mL of brine The ether layers were dried over MgSO4 concentrated in vacuo affording 5.7 g of crude product

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

Procedure: Reaction of 3-((E)-3-dimethylamino-acryloyl)-1-(3-methansulfonyl-phenyl)-1H-pyridazin-4-one (A-7) and (3-chloro-2-methyl-phenyl)-hydrazine according to example 43 gave the desired product. MS: M=441.0 (M)+

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

Procedure: 1.44 g (10 mmole) of sec-butyl isothiocyanate were added to 1.56 g (10 mmole) of 3-chloro-2-methylphenyl hydrazine dissolved in 120 ml of toluene, and the mixture was refluxed for 2 hours and then evaporated. The remanence was stirred with a small amount of hexane, separated by filtration and dried. the mixture was refluxed for 2 hours evaporated separated by filtration dried

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

Procedure: The title compound was prepared in accordance with the general method of example 25b) from a) (3-chloro-2-methyl-phenyl)-hydrazine and ethyl pyruvate.