(4-bromophenyl)methylhydrazine

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 17.5 g of β-amino-β-ethoxyacrylic acid ethyl ester and 20 g of 4-bromobenzylhydrazine, on stirring for 5 hours in alcohol at 50° and working up as described in Example 1, yield 15.6 g of the compound identified above, corresponding to 58% of theory, as colorless crystals of melting point 139°.

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9.2 g of metallic sodium are dissolved in 200 ml of ethanol. A mixture of 25 g of cyanoacetic acid ethyl ester and 35 g of p-bromobenzylhydrazine in 50 ml of ethanol is then added at room temperature. The mixture is warmed to 60° C for 2 hours, the substance which was precipitated is filtered off and the filtrate is evaporated. The residue is taken up with water, the mixture is shaken with ether and the aqueous phase is acidified with dilute acetic acid. The crude product is purified by twice recrystallising it from alcohol. is then added at room temperature the substance which was precipitated is filtered off the filtrate is evaporated The crude product is purified by twice recrystallising it from alcohol

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9.2 g of metallic sodium are dissolved in 200 ml of ethanol. A mixture of 25 g of cyanoacetic acid ethyl ester and 35 g of p-bromobenzylhydrazine in 50 ml of ethanol is then added at room temperature. The mixture is warmed to 60° C for 2 hours, the substance which was precipitated is filtered off and the filtrate is evaporated. The residue is taken up with water, the mixture is shaken with ether and the aqueous phase is acidified with dilute acetic acid. The crude product is purified by twice recrystallising it from alcohol. is then added at room temperature the substance which was precipitated is filtered off the filtrate is evaporated The crude product is purified by twice recrystallising it from alcohol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 17.5 g of β-amino-β-ethoxyacrylic acid ethyl ester and 20 g of 4-bromobenzylhydrazine, on stirring for 5 hours in alcohol at 50° and working up as described in Example 1, yield 15.6 g of the compound identified above, corresponding to 58% of theory, as colorless crystals of melting point 139°.

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9.2 g of metallic sodium are dissolved in 200 ml of ethanol. A mixture of 25 g of cyanoacetic acid ethyl ester and 35 g of p-bromobenzylhydrazine in 50 ml of ethanol is then added at room temperature. The mixture is warmed to 60° C for 2 hours, the substance which was precipitated is filtered off and the filtrate is evaporated. The residue is taken up with water, the mixture is shaken with ether and the aqueous phase is acidified with dilute acetic acid. The crude product is purified by twice recrystallising it from alcohol. is then added at room temperature the substance which was precipitated is filtered off the filtrate is evaporated The crude product is purified by twice recrystallising it from alcohol

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9.2 g of metallic sodium are dissolved in 200 ml of ethanol. A mixture of 25 g of cyanoacetic acid ethyl ester and 35 g of p-bromobenzylhydrazine in 50 ml of ethanol is then added at room temperature. The mixture is warmed to 60° C for 2 hours, the substance which was precipitated is filtered off and the filtrate is evaporated. The residue is taken up with water, the mixture is shaken with ether and the aqueous phase is acidified with dilute acetic acid. The crude product is purified by twice recrystallising it from alcohol. is then added at room temperature the substance which was precipitated is filtered off the filtrate is evaporated The crude product is purified by twice recrystallising it from alcohol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 17.5 g of β-amino-β-ethoxyacrylic acid ethyl ester and 20 g of 4-bromobenzylhydrazine, on stirring for 5 hours in alcohol at 50° and working up as described in Example 1, yield 15.6 g of the compound identified above, corresponding to 58% of theory, as colorless crystals of melting point 139°.

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9.2 g of metallic sodium are dissolved in 200 ml of ethanol. A mixture of 25 g of cyanoacetic acid ethyl ester and 35 g of p-bromobenzylhydrazine in 50 ml of ethanol is then added at room temperature. The mixture is warmed to 60°C for 2 hours, the substance which was precipitated is filtered off and the filtrate is evaporated. The residue is taken up with water, the mixture is shaken with ether and the aqueous phase is acidified with dilute acetic acid. The crude product is purified by twice recrystallising it from alcohol. is then added at room temperature the substance which was precipitated is filtered off the filtrate is evaporated The crude product is purified by twice recrystallising it from alcohol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Cbz-(L)-Valine (1.04 g, 4.14 mmol) was dissolved in EtOAc (50 mL) and EDAC (0.870 g, 4.54 mmol), HOBT (0.610 g, 4.51 mmol), and NMM (0.500 mL, 4.55 mmol) were added. The reaction mixture was stirred at room temperature for 30 min and then 4-bromo-benzylhydrazine (1.00 g, 4.97 mmol) in EtOAc (5 mL) was added and the stirring was continued for 2 h. After evaporation of the solvent, CHCl3 was added and the solution was washed with saturated NaHCO3 (aq.) and brine followed by drying (Na2SO4), filtration and evaporation of the organic solvent. The crude product was purified by column chromatography (silica, CHCl3/MeOH, 100:0-95:5) yielding the title compound (1.42 g, 79%) as a white solid. the stirring was continued for 2 h After evaporation of the solvent, CHCl3 was added the solution was washed with saturated NaHCO3 (aq.) and brine by drying (Na2SO4), filtration and evaporation of the organic solvent The crude product was purified by column chromatography (silica, CHCl3/MeOH, 100:0-95:5)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-(Methoxycarbonyl)-(L)-tert-leucine (J. Med. Chem., 41, 3387-3401, 1998) (1.74 g, 9.20 mmol) was dissolved in EtOAc (50 mL) and EDAC (1.94 g, 10.1 mmol), HOBT (1.37 g, 10.1 mmol), and NMM (1.11 mL, 10.1 mmol) were added. The reaction mixture was stirred at room temperature for 30 min and then 4-bromo-benzylhydrazine (prepared as described in Zh. Org. Khim., 28, 43-50, 1992) (2.31 g, 11.5 mmol) in EtOAc (20 mL) was added and the stirring was continued over night. The reaction mixture was washed with saturated NaHCO3 (aq.), H2O and brine and then the organic phase was dried (Na2SO4), filtered and evaporated. The crude product was purified by column chromatography (silica, CHCl3/MeOH, 100:0-96:4) yielding the title compound (1.85 g, 54%) as a white solid. the stirring was continued over night The reaction mixture was washed with saturated NaHCO3 (aq.), H2O and brine the organic phase was dried (Na2SO4) filtered evaporated The crude product was purified by column chromatography (silica, CHCl3/MeOH, 100:0-96:4)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 17.5 g of β-amino-β-ethoxyacrylic acid ethyl ester and 20 g of 4-bromobenzylhydrazine, on stirring for 5 hours in alcohol at 50° and working up as described in Example 1, yield 15.6 g of the compound identified above, corresponding to 58% of theory, as colorless crystals of melting point 139°.

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9.2 g of metallic sodium are dissolved in 200 ml of ethanol. A mixture of 25 g of cyanoacetic acid ethyl ester and 35 g of p-bromobenzylhydrazine in 50 ml of ethanol is then added at room temperature. The mixture is warmed to 60° C for 2 hours, the substance which was precipitated is filtered off and the filtrate is evaporated. The residue is taken up with water, the mixture is shaken with ether and the aqueous phase is acidified with dilute acetic acid. The crude product is purified by twice recrystallising it from alcohol. is then added at room temperature the substance which was precipitated is filtered off the filtrate is evaporated The crude product is purified by twice recrystallising it from alcohol