O-(2-aminoethyl)hydroxylamine;dihydrochloride

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

Procedure: A mixture of 1-[1-(4-oxo-4-phenylbutyl)-4-piperidinyl]-1,3-dihydro-2-benzimidazolone (3.85 g), O-(2-aminoethyl)hydroxylamine dihydrochloride (1.89 g), 3 equivalents of pyridine, and absolute ethanol (75 ml) was heated under reflux, under nitrogen, with stirring, for three hrs. The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate. The layers were separated and the aqueous phase extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was taken up in toluene and evaporated. The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide). The appropriate fractions were collected and evaporated. The residue was dissolved in absolute ethanol and treated with ethereal hydrogen chloride. The solvent was evaporated and the residue was taken up in hot 2-propanol and chilled. The precipitate was collected and recrystallized from 2-propanol and then twice from ethanol/ether to give 1.5 g (29%) of product, mp 175°-180° C. (dec). was heated under reflux, under nitrogen The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate The layers were separated the aqueous phase extracted with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered the filtrate was evaporated evaporated The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide) The appropriate fractions were collected evaporated The residue was dissolved in absolute ethanol treated with ethereal hydrogen chloride The solvent was evaporated chilled The precipitate was collected recrystallized from 2-propanol

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

Procedure: A mixture of 1-[1-(4-oxo-4-phenylbutyl)-4-piperidinyl]-1,3-dihydro-2-benzimidazolone (3.85 g), O-(2-aminoethyl)hydroxylamine dihydrochloride (1.89 g), 3 equivalents of pyridine, and absolute ethanol (75 ml) was heated under reflux, under nitrogen, with stirring, for three hrs. The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate. The layers were separated and the aqueous phase extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was taken up in toluene and evaporated. The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide). The appropriate fractions were collected and evaporated. The residue was dissolved in absolute ethanol and treated with ethereal hydrogen chloride. The solvent was evaporated and the residue was taken up in hot 2-propanol and chilled. The precipitate was collected and recrystallized from 2-propanol and then twice from ethanol/ether to give 1.5 g (29%) of product, mp 175°-180° C. (dec). was heated under reflux, under nitrogen The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate The layers were separated the aqueous phase extracted with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered the filtrate was evaporated evaporated The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide) The appropriate fractions were collected evaporated The residue was dissolved in absolute ethanol treated with ethereal hydrogen chloride The solvent was evaporated chilled The precipitate was collected recrystallized from 2-propanol

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

Procedure: A mixture of 1-{1-[4-oxo-4-(4-chlorophenyl)butyl]-4-piperidinyl}-1,3-dihydro-2-benzimidazolone (3.00 g), O-(2-aminoethyl)hydroxylamine dihydrochloride (1.35 g), 3 equivalents of pyridine, and absolute ethanol (75 ml) was heated under reflux, under nitrogen, with stirring, for three hrs. The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate. The layers were separated and the aqueous phase extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was taken up in toluene and evaporated. The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide). The appropriate fractions were collected and evaporated. The residue was dissolved in absolute ethanol and treated with ethereal hydrogen chloride. The solvent was evaporated, and the residue was taken up in hot 2-propanol and chilled. The precipitate was collected and recrystallized twice from absolute ethanol/ether to give 2.1 g (53%) of product, mp 140°-145° C. (dec). was heated under reflux, under nitrogen The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate The layers were separated the aqueous phase extracted with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered the filtrate was evaporated evaporated The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide) The appropriate fractions were collected evaporated The residue was dissolved in absolute ethanol treated with ethereal hydrogen chloride The solvent was evaporated chilled The precipitate was collected recrystallized twice from absolute ethanol/ether

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

Procedure: A mixture of 1-{1-[4-oxo-4-(4-chlorophenyl)butyl]-4-piperidinyl}-1,3-dihydro-2-benzimidazolone (3.00 g), O-(2-aminoethyl)hydroxylamine dihydrochloride (1.35 g), 3 equivalents of pyridine, and absolute ethanol (75 ml) was heated under reflux, under nitrogen, with stirring, for three hrs. The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate. The layers were separated and the aqueous phase extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was taken up in toluene and evaporated. The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide). The appropriate fractions were collected and evaporated. The residue was dissolved in absolute ethanol and treated with ethereal hydrogen chloride. The solvent was evaporated, and the residue was taken up in hot 2-propanol and chilled. The precipitate was collected and recrystallized twice from absolute ethanol/ether to give 2.1 g (53%) of product, mp 140°-145° C. (dec). was heated under reflux, under nitrogen The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate The layers were separated the aqueous phase extracted with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered the filtrate was evaporated evaporated The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide) The appropriate fractions were collected evaporated The residue was dissolved in absolute ethanol treated with ethereal hydrogen chloride The solvent was evaporated chilled The precipitate was collected recrystallized twice from absolute ethanol/ether

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-[4-(4-fluorobenzoyl)-1-piperdinyl]-1-phenyl-1-butanone (5.00 g) , O-(2-aminoethyl)hydroxylamine dihydrochloride (2.21 g), 3 equivalents of pyridine, and absolute ethanol (75 ml) was stirred at 60° C., overnight, under nitrogen. The reaction mixture was evaporated, toluene was added and evaporated. The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate. The layers were separated and the aqueous phase extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide). The appropriate fractions were collected and evaporated. The residue was dissolved in absolute ethanol and treated with ethereal hydrogen chloride. Diethyl ether was added. The precipitate was collected and recrystallized twice from absolute ethanol/ether to give 2.3 g (34%) of product, mp 110°-115° C. (dec). The reaction mixture was evaporated toluene was added evaporated The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate The layers were separated the aqueous phase extracted with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered the filtrate was evaporated The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide) The appropriate fractions were collected evaporated The residue was dissolved in absolute ethanol treated with ethereal hydrogen chloride Diethyl ether was added The precipitate was collected recrystallized twice from absolute ethanol/ether

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-[4-(4-fluorobenzoyl)-1-piperdinyl]-1-phenyl-1-butanone (5.00 g) , O-(2-aminoethyl)hydroxylamine dihydrochloride (2.21 g), 3 equivalents of pyridine, and absolute ethanol (75 ml) was stirred at 60° C., overnight, under nitrogen. The reaction mixture was evaporated, toluene was added and evaporated. The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate. The layers were separated and the aqueous phase extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide). The appropriate fractions were collected and evaporated. The residue was dissolved in absolute ethanol and treated with ethereal hydrogen chloride. Diethyl ether was added. The precipitate was collected and recrystallized twice from absolute ethanol/ether to give 2.3 g (34%) of product, mp 110°-115° C. (dec). The reaction mixture was evaporated toluene was added evaporated The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate The layers were separated the aqueous phase extracted with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered the filtrate was evaporated The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide) The appropriate fractions were collected evaporated The residue was dissolved in absolute ethanol treated with ethereal hydrogen chloride Diethyl ether was added The precipitate was collected recrystallized twice from absolute ethanol/ether

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

Procedure: A mixture of 5-(1-(1H)-imidazolyl)-1-(4-trifluoromethylphenyl)-1-pentanone (11.5 g), O-(2-aminoethyl)hydroxylamine dihydrochloride (5.78 g), 3 equivalents of pyridine, and absolute ethanol (75 ml) was heated under reflux, under nitrogen, with stirring, for three hrs. The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate. The layers were separated and the aqueous phase extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was taken up in toluene and evaporated. The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide). The appropriate fractions were collected and evaporated. The residue was dissolved in absolute ethanol and treated with ethereal hydrogen chloride. Diethyl ether was added. The precipitate was collected and recrystallized twice from absolute ethanol/ether to give 3.3 g (20%) of product, mp 115°-120° C. (dec). was heated under reflux, under nitrogen The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate The layers were separated the aqueous phase extracted with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered the filtrate was evaporated evaporated The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide) The appropriate fractions were collected evaporated The residue was dissolved in absolute ethanol treated with ethereal hydrogen chloride Diethyl ether was added The precipitate was collected recrystallized twice from absolute ethanol/ether

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

Procedure: A mixture of 5-(1-(1H)-imidazolyl)-1-(4-trifluoromethylphenyl)-1-pentanone (11.5 g), O-(2-aminoethyl)hydroxylamine dihydrochloride (5.78 g), 3 equivalents of pyridine, and absolute ethanol (75 ml) was heated under reflux, under nitrogen, with stirring, for three hrs. The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate. The layers were separated and the aqueous phase extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was taken up in toluene and evaporated. The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide). The appropriate fractions were collected and evaporated. The residue was dissolved in absolute ethanol and treated with ethereal hydrogen chloride. Diethyl ether was added. The precipitate was collected and recrystallized twice from absolute ethanol/ether to give 3.3 g (20%) of product, mp 115°-120° C. (dec). was heated under reflux, under nitrogen The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate The layers were separated the aqueous phase extracted with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered the filtrate was evaporated evaporated The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide) The appropriate fractions were collected evaporated The residue was dissolved in absolute ethanol treated with ethereal hydrogen chloride Diethyl ether was added The precipitate was collected recrystallized twice from absolute ethanol/ether

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

Procedure: A mixture of 1-(3,4-dichlorophenyl)-4-(1-(1H)-imidazolyl)-1-butanone (2.29 g), O-(2-aminoethyl)hydroxylamine dihydrochloride (1.45 g), 3 equivalents of pyridine, and absolute ethanol (75 ml) was heated under reflux, under nitrogen, with stirring, for three hrs. The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate. The layers were separated and the aqueous phase extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was taken up in toluene and evaporated. The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide). The appropriate fractions were collected and evaporated. The residue was dissolved in absolute ethanol and treated with ethereal hydrogen chloride. Diethyl ether was added. The precipitate was collected and recrystallized twice from absolute ethanol/ether to give 1.1 g (33%) of product, mp 205°-208° C. (dec). was heated under reflux, under nitrogen The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate The layers were separated the aqueous phase extracted with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered the filtrate was evaporated evaporated The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide) The appropriate fractions were collected evaporated The residue was dissolved in absolute ethanol treated with ethereal hydrogen chloride Diethyl ether was added The precipitate was collected recrystallized twice from absolute ethanol/ether

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

Procedure: A mixture of 1-(3,4-dichlorophenyl)-4-(1-(1H)-imidazolyl)-1-butanone (2.29 g), O-(2-aminoethyl)hydroxylamine dihydrochloride (1.45 g), 3 equivalents of pyridine, and absolute ethanol (75 ml) was heated under reflux, under nitrogen, with stirring, for three hrs. The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate. The layers were separated and the aqueous phase extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was taken up in toluene and evaporated. The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide). The appropriate fractions were collected and evaporated. The residue was dissolved in absolute ethanol and treated with ethereal hydrogen chloride. Diethyl ether was added. The precipitate was collected and recrystallized twice from absolute ethanol/ether to give 1.1 g (33%) of product, mp 205°-208° C. (dec). was heated under reflux, under nitrogen The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate The layers were separated the aqueous phase extracted with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered the filtrate was evaporated evaporated The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide) The appropriate fractions were collected evaporated The residue was dissolved in absolute ethanol treated with ethereal hydrogen chloride Diethyl ether was added The precipitate was collected recrystallized twice from absolute ethanol/ether

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

Procedure: A mixture of 1-(4-fluorophenyl)-4-(2-methyl-1-(1H)-imidazolyl)-1-butanone (3.00 g), O-(2-aminoethyl)hydroxylamine dihydrochloride (2.18 g), 3 equivalents of pyridine, and absolute ethanol (75 ml) was heated under reflux, under nitrogen, with stirring, for three hrs. The reaction mixture was evaporated, toluene was added and evaporated. The residue was partitioned between 10% sodium hydroxide solution and ethyl acetate. The layers were separated and the aqueous phase extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide). The appropriate fractions were collected and concentrated. The residue was dissolved in absolute ethanol and treated with ethereal hydrogen chloride. Diethyl ether was added. The precipitate was collected and recrystallized from absolute ethanol/ether to give 3.2 g (70%) of product, mp 219°-221° C. (dec). was heated under reflux, under nitrogen The reaction mixture was evaporated toluene was added evaporated The residue was partitioned between 10% sodium hydroxide solution and ethyl acetate The layers were separated the aqueous phase extracted with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered the filtrate was evaporated The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide) The appropriate fractions were collected concentrated The residue was dissolved in absolute ethanol treated with ethereal hydrogen chloride Diethyl ether was added The precipitate was collected recrystallized from absolute ethanol/ether

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

Procedure: A mixture of 1-(4-fluorophenyl)-4-(2-methyl-1-(1H)-imidazolyl)-1-butanone (3.00 g), O-(2-aminoethyl)hydroxylamine dihydrochloride (2.18 g), 3 equivalents of pyridine, and absolute ethanol (75 ml) was heated under reflux, under nitrogen, with stirring, for three hrs. The reaction mixture was evaporated, toluene was added and evaporated. The residue was partitioned between 10% sodium hydroxide solution and ethyl acetate. The layers were separated and the aqueous phase extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide). The appropriate fractions were collected and concentrated. The residue was dissolved in absolute ethanol and treated with ethereal hydrogen chloride. Diethyl ether was added. The precipitate was collected and recrystallized from absolute ethanol/ether to give 3.2 g (70%) of product, mp 219°-221° C. (dec). was heated under reflux, under nitrogen The reaction mixture was evaporated toluene was added evaporated The residue was partitioned between 10% sodium hydroxide solution and ethyl acetate The layers were separated the aqueous phase extracted with ethyl acetate The combined organic extracts were dried over anhydrous sodium sulfate filtered the filtrate was evaporated The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide) The appropriate fractions were collected concentrated The residue was dissolved in absolute ethanol treated with ethereal hydrogen chloride Diethyl ether was added The precipitate was collected recrystallized from absolute ethanol/ether