N'-hydroxypropanimidamide

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

実験手順: Dichloroethane (5 ml), thionyl chloride (0.65 g, 5.5 mmol) and dimethylformamide (0.05 ml) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetic acid (1.57 g, 5 mmol), and the mixture was stirred under reflux for 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, pyridine (3 ml) and 1-hydroxyimino-l-propylamine (0.88 g, 10 mmol) were added to the residue, and the mixture was stirred under reflux for 0.5 hours. After completion of the reaction, ether (150 ml) was added, and the mixture was washed with 1N hydrochloric acid (150 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl 3-ethyl-1,2,4-oxadiazol-5-yl ketone O-methyloxime (0.63 g, 34.5%) as colorless crystals. under reflux for 2 hours After completion of the reaction were added to the residue the mixture was stirred under reflux for 0.5 hours was added the mixture was washed with 1N hydrochloric acid (150 ml) twice The ether layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) recrystallized from ethyl acetate/n-hexane

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

実験手順: Dichloroethane (5 ml), thionyl chloride (0.65 g, 5.5 mmol) and dimethylformamide (0.05 ml) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetic acid (1.57 g, 5 mmol), and the mixture was stirred under reflux for 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, pyridine (3 ml) and 1-hydroxyimino-l-propylamine (0.88 g, 10 mmol) were added to the residue, and the mixture was stirred under reflux for 0.5 hours. After completion of the reaction, ether (150 ml) was added, and the mixture was washed with 1N hydrochloric acid (150 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl 3-ethyl-1,2,4-oxadiazol-5-yl ketone O-methyloxime (0.63 g, 34.5%) as colorless crystals. under reflux for 2 hours After completion of the reaction were added to the residue the mixture was stirred under reflux for 0.5 hours was added the mixture was washed with 1N hydrochloric acid (150 ml) twice The ether layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) recrystallized from ethyl acetate/n-hexane

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

実験手順: At 40° C., a suspension of 26.0 g of carbonyldiimidazole in 250 ml of THF is added to a solution of 65.7 g of phthalimidoacetic acid in 500 ml of THF (absolute). After about one hour, no release of gas can be observed any longer. At this point in time, a solution of 28.2 g of propionamidoxime in 50 ml of THF-- is added, and the mixture is stirred at room temperature for 24 hours. After the precipitate has been filtered off, the filtrate is concentrated under vacuum and, after addition of 500 ml of dry xylene, is heated under reflux for 6 hours on a water trap. The still hot solution is separated from the oily residue and concentrated under vacuum. Crystallization from EtOH yields 31.5 g (76.5%, based on carbonyldiimidazole) of oxadiazole having a melting point of 106°-107° C. After the precipitate has been filtered off the filtrate is concentrated under vacuum after addition of 500 ml of dry xylene is heated under reflux for 6 hours on a water trap The still hot solution is separated from the oily residue concentrated under vacuum Crystallization from EtOH yields 31.5 g (76.5%, based on carbonyldiimidazole) of oxadiazole having a melting point of 106°-107° C.

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

実験手順: At 40° C., a suspension of 26.0 g of carbonyldiimidazole in 250 ml of THF is added to a solution of 65.7 g of phthalimidoacetic acid in 500 ml of THF (absolute). After about one hour, no release of gas can be observed any longer. At this point in time, a solution of 28.2 g of propionamidoxime in 50 ml of THF-- is added, and the mixture is stirred at room temperature for 24 hours. After the precipitate has been filtered off, the filtrate is concentrated under vacuum and, after addition of 500 ml of dry xylene, is heated under reflux for 6 hours on a water trap. The still hot solution is separated from the oily residue and concentrated under vacuum. Crystallization from EtOH yields 31.5 g (76.5%, based on carbonyldiimidazole) of oxadiazole having a melting point of 106°-107° C. After the precipitate has been filtered off the filtrate is concentrated under vacuum after addition of 500 ml of dry xylene is heated under reflux for 6 hours on a water trap The still hot solution is separated from the oily residue concentrated under vacuum Crystallization from EtOH yields 31.5 g (76.5%, based on carbonyldiimidazole) of oxadiazole having a melting point of 106°-107° C.

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

実験手順: Dichloroethane (5 ml), thionyl chloride (0.65 g, 5.5 mmol) and N,N-dimethylformamide (0.05 ml) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetic acid (1.57 g, 5 mmol), and the mixture was stirred under reflux for 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, pyridine (3 ml) and 1-hydroxyimino-1-propylamine (0.88 g, 10 mmol) were added to the residue, and the mixture was stirred under reflux for 0.5 hours. After completion of the reaction, ether (150 ml) was added, and the mixture was washed with 1N hydrochloric acid (150 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl 3-ethyl-1,2,4-oxadiazol-5-yl ketone O-methyloxime (0.63 g, 34.5%) as colorless crystals. under reflux for 2 hours After completion of the reaction were added to the residue the mixture was stirred under reflux for 0.5 hours was added the mixture was washed with 1N hydrochloric acid (150 ml) twice The ether layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) recrystallized from ethyl acetate/n-hexane

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

実験手順: A solution of 0.36 g of 4-methoxymethyl-5-morpholinomethyl-beta-carboline-3-carboxylic acid (prepared according to example 4) in 10 ml of absolute dimethylformamide is mixed with 0.2 g of carbonyldiimidazole and stirred for 30 minutes at 60° C. Then 0.4 g of propioamidoxime in 2 ml of DMF is added and the reaction mixture heated to 100° C. for 3 hours. After distilling off of the solvent in a vacuum, the residue is mixed with 20 ml of xylene and refluxed for 3 hours on the water separator, the reaction mixture is filtered hot, the filtrate is concentrated and chromatographed on silica gel. 0.25 g (60%) of oxadiazole derivative is obtained. Melting point 161°-163° C. the reaction mixture heated to 100° C. for 3 hours After distilling off of the solvent in a vacuum the residue is mixed with 20 ml of xylene refluxed for 3 hours on the water separator the reaction mixture is filtered hot the filtrate is concentrated chromatographed on silica gel

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

実験手順: A solution of 0.36 g of 4-methoxymethyl-5-morpholinomethyl-beta-carboline-3-carboxylic acid (prepared according to example 4) in 10 ml of absolute dimethylformamide is mixed with 0.2 g of carbonyldiimidazole and stirred for 30 minutes at 60° C. Then 0.4 g of propioamidoxime in 2 ml of DMF is added and the reaction mixture heated to 100° C. for 3 hours. After distilling off of the solvent in a vacuum, the residue is mixed with 20 ml of xylene and refluxed for 3 hours on the water separator, the reaction mixture is filtered hot, the filtrate is concentrated and chromatographed on silica gel. 0.25 g (60%) of oxadiazole derivative is obtained. Melting point 161°-163° C. the reaction mixture heated to 100° C. for 3 hours After distilling off of the solvent in a vacuum the residue is mixed with 20 ml of xylene refluxed for 3 hours on the water separator the reaction mixture is filtered hot the filtrate is concentrated chromatographed on silica gel

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

実験手順: The title compound free base (17 g, 77%) was prepared from methyl quinuclidine-3-carboxylate (18.0 g, 0.11 mol), propionamide oxime (14 g, 0.16 mol) and sodium hydride (7 g of a 55% oil dispersion, 0.16 mol) in anhydrous tetrahydrofuran (350 mL). The hydrogen oxalate salt had mp 113°-115° C. (propan-2-ol). Rf 0.3 in dichloromethane/methanol (50:1) on alumina plates. (Found: C, 52.25; H, 6.41; N, 14.07. C11H17N3O.C2H2O4 requires C, 52.52; H, 6.44; N, 14.13%).

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

実験手順: The title compound free base (17 g, 77%) was prepared from methyl quinuclidine-3-carboxylate (18.0 g, 0.11 mol), propionamide oxime (14 g, 0.16 mol) and sodium hydride (7 g of a 55% oil dispersion, 0.16 mol) in anhydrous tetrahydrofuran (350 mL). The hydrogen oxalate salt had mp 113°-115° C. (propan-2-ol). Rf 0.3 in dichloromethane/methanol (50:1) on alumina plates. (Found: C, 52.25; H, 6.41; N, 14.07. C11H17N3O.C2H2O4 requires C, 52.52; H, 6.44; N, 14.13%).

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 0.05 g of methyl 3-chloro-5-(3,3-dichloroprop-2-enyloxy)-2-[3-(5-trifluoromethylpyrid-2-yloxy)propyloxy]benzoate and 0.028 g of propionamidoxime were dissolved in 1 ml of anhydrous ethanol. A solution of 0.008 g of sodium in 0.5 ml of ethanol was added to this solution. The mixture was stirred at 40° C. for 2 hours and at room temperature for 20 hours. The mixture was then concentrated, and diethyl ether and water were added. After shaking, the ether phase was isolated, dried and concentrated under reduced pressure, and the crude product was purified chromatographically. Yield: 0.017 g (32%) The mixture was then concentrated diethyl ether and water were added After shaking the ether phase was isolated dried concentrated under reduced pressure the crude product was purified chromatographically

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 0.05 g of methyl 3-chloro-5-(3,3-dichloroprop-2-enyloxy)-2-[3-(5-trifluoromethylpyrid-2-yloxy)propyloxy]benzoate and 0.028 g of propionamidoxime were dissolved in 1 ml of anhydrous ethanol. A solution of 0.008 g of sodium in 0.5 ml of ethanol was added to this solution. The mixture was stirred at 40° C. for 2 hours and at room temperature for 20 hours. The mixture was then concentrated, and diethyl ether and water were added. After shaking, the ether phase was isolated, dried and concentrated under reduced pressure, and the crude product was purified chromatographically. Yield: 0.017 g (32%) The mixture was then concentrated diethyl ether and water were added After shaking the ether phase was isolated dried concentrated under reduced pressure the crude product was purified chromatographically

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

実験手順: Dichloroethane (5 ml), thionyl chloride (0.65 g, 5.5 mmol) and dimethylformamide (0.05 ml) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetic acid (1.57 g, 5 mmol), and the mixture was stirred under reflux for 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, pyridine (3 ml) and 1-hydroxyimino-l-propylamine (0.88 g, 10 mmol) were added to the residue, and the mixture was stirred under reflux for 0.5 hours. After completion of the reaction, ether (150 ml) was added, and the mixture was washed with 1N hydrochloric acid (150 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl 3-ethyl-1,2,4-oxadiazol-5-yl ketone O-methyloxime (0.63 g, 34.5%) as colorless crystals. under reflux for 2 hours After completion of the reaction were added to the residue the mixture was stirred under reflux for 0.5 hours was added the mixture was washed with 1N hydrochloric acid (150 ml) twice The ether layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) recrystallized from ethyl acetate/n-hexane