butanehydrazide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: Added to a solution of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid (0.40 g, 1.05 mmol), N-butanoyl-hydrazine (0.11 g, 1.05 mmol) and EDCI (0.24 g, 1.26 mmol) dissolved in DCM (11 ml), was DMAP (0.15 g, 1.26 mmol) in one portion at room temperature. The reaction mixture was stirred at room temperature for 6 hrs, and then treated with 10% aq. HCl. The organic layer was collected, and evaporated under a vacuum. The crude mixture was further purified by preparative HPLC, to obtain 0.38 g (0.81 mmol, 77%) of the title compound as yellow solid. at room temperature The organic layer was collected evaporated under a vacuum The crude mixture was further purified by preparative HPLC

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

実験手順: Added to a solution of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid (0.40 g, 1.05 mmol), N-butanoyl-hydrazine (0.11 g, 1.05 mmol) and EDCI (0.24 g, 1.26 mmol) dissolved in DCM (11 ml), was DMAP (0.15 g, 1.26 mmol) in one portion at room temperature. The reaction mixture was stirred at room temperature for 6 hrs, and then treated with 10% aq. HCl. The organic layer was collected, and evaporated under a vacuum. The crude mixture was further purified by preparative HPLC, to obtain 0.38 g (0.81 mmol, 77%) of the title compound as yellow solid. at room temperature The organic layer was collected evaporated under a vacuum The crude mixture was further purified by preparative HPLC

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

実験手順: A mixture of 5.20 gm (0.0335 mole) of 4-acetyl-3-chloropyridine, 3.43 gm (0.0336 mole) of butyric acid hydrazide and 100 ml of ethanol was refluxed 18 hr. The mixture was chilled in the freezer. The solid which separated was collected to give 2.01 gm (25%) of white solid having a melting point of 103.8° C. was refluxed 18 hr The mixture was chilled in the freezer The solid which separated was collected

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

実験手順: A mixture of 5.48 gm (0.04 mole) of 4-acetylpyridine 1-oxide, 4.09 gm (0.04 mole) of butyric acid hydrazide and 100 ml of absolute ethanol is refluxed 6 hours. The reactions mixture is evaporated in vacuo to give a solid. The crude product is crystallized from ethyl acetate/ethanol to yield 7.41 gm (84%) of the title compound; mp 209.7°. is refluxed 6 hours The reactions mixture is evaporated in vacuo to give a solid The crude product is crystallized from ethyl acetate/ethanol

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

実験手順: To a solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.25 g, 0.90 mmol) in dry DCM (40 mL) were added butanehydrazide 234 (0.14 g, 1.35 mmol), 1-hydroxybenzotriazole (0.19 g, 1.35 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.26 g, 1.35 mmol) and 4-(dimethylamino)pyridine (0.16 g, 1.35 mmol) at room temperature. The reaction mixture was stirred at room temperature overnight, and then concentrated under vacuum. The residue was purified by column chromatography to give (2R,5S)-6-(benzyloxy)-N-butanoyl-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide 235 (0.31 g, 95%) as a white solid. concentrated under vacuum The residue was purified by column chromatography

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

実験手順: To a solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.25 g, 0.90 mmol) in dry DCM (40 mL) were added butanehydrazide 234 (0.14 g, 1.35 mmol), 1-hydroxybenzotriazole (0.19 g, 1.35 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.26 g, 1.35 mmol) and 4-(dimethylamino)pyridine (0.16 g, 1.35 mmol) at room temperature. The reaction mixture was stirred at room temperature overnight, and then concentrated under vacuum. The residue was purified by column chromatography to give (2R,5S)-6-(benzyloxy)-N-butanoyl-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide 235 (0.31 g, 95%) as a white solid. concentrated under vacuum The residue was purified by column chromatography

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

実験手順: To a solution of 5.0 g (47.0 mmol) cyanogen bromide in 50 ml of methanol was added dropwise over a period of 30 min a solution of 4.80 g (47.0 mmol) butyric acid hydrazide in 50 ml of methanol. The mixture was then refluxed for 15 min, and then concentrated in vacuo till cristallisation began. The cristals (9 g) were filtered off, taken up in 60 ml of ethanol. Then 5 g of finely powdered potassium carbonate were added and the suspension was stirred for 5 min at room temperature. The resulting orange suspension was filtered, and the filtrate was concentrated in vacuo. The resulting orange powder (5.5 g) was purified by flash chromatography on silicagel with a 80:10:1 mixture of methylene chloride/methanol/28% ammonia as eluent to yield 3.95 g (31.1 mmol, 66%) of 5-propyl-[1,3,4]oxadiazol-2-ylamine as white cristals, MS: m/e=127 (M+). The mixture was then refluxed for 15 min concentrated in vacuo till cristallisation The cristals (9 g) were filtered off Then 5 g of finely powdered potassium carbonate were added The resulting orange suspension was filtered the filtrate was concentrated in vacuo The resulting orange powder (5.5 g) was purified by flash chromatography on silicagel with a 80:10:1 mixture of methylene chloride/methanol/28% ammonia as eluent

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

実験手順: To a solution of 5.0 g (47.0 mmol) cyanogen bromide in 50 ml of methanol was added dropwise over a period of 30 min a solution of 4.80 g (47.0 mmol) butyric acid hydrazide in 50 ml of methanol. The mixture was then refluxed for 15 min, and then concentrated in vacuo till cristallisation began. The cristals (9 g) were filtered off, taken up in 60 ml of ethanol. Then 5 g of finely powdered potassium carbonate were added and the suspension was stirred for 5 min at room temperature. The resulting orange suspension was filtered, and the filtrate was concentrated in vacuo. The resulting orange powder (5.5 g) was purified by flash chromatography on silicagel with a 80:10:1 mixture of methylene chloride/methanol/28% ammonia as eluent to yield 3.95 g (31.1 mmol, 66%) of 5-propyl-[1,3,4]oxadiazol-2-ylamine as white cristals, MS: m/e=127 (M+). The mixture was then refluxed for 15 min concentrated in vacuo till cristallisation The cristals (9 g) were filtered off Then 5 g of finely powdered potassium carbonate were added The resulting orange suspension was filtered the filtrate was concentrated in vacuo The resulting orange powder (5.5 g) was purified by flash chromatography on silicagel with a 80:10:1 mixture of methylene chloride/methanol/28% ammonia as eluent

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

実験手順: A mixture of 10 g. of 3-chloro-6-phenylpyridazine, 11.2 g. of butyric acid hydrazide and 100 ml. of n-butanol is heated at reflux for 40 hours. The solution is cooled and the precipitate is filtered and washed with petroleum ether and water. The filtrate is concentrated to an oil which forms a precipitate upon the addition of petroleum ether. The precipitate is collected and washed with petroleum ether and water. The solids are combined and recrystallized from 30 ml. of ethanol giving 3-n-propyl-6-phenyl-1,2,4-triazolo[4,3-b]pyridazine as crystals, m.p. 123°-125° C. A mixture of 10 g at reflux for 40 hours The solution is cooled the precipitate is filtered washed with petroleum ether and water The filtrate is concentrated to an oil which upon the addition of petroleum ether The precipitate is collected washed with petroleum ether and water recrystallized from 30 ml

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

実験手順: A suspension of intermediate (13) (0.0102 mole) in n-butanol (200 ml) was treated with butanoic acid hydrazide (0.0254 mole), stirred for 10 minutes, and then heated to reflux for 10 days. The reaction was cooled, concentrated in vacuo, distributed between DCM and distilled water. The concentrated organic phase was subjected to reverse phase preparatory column chromatography to give 1-acetyl-2,3-dihydro-2-(5-propyl-1H-1,2,4-triazol-3-yl)-1H-indole (compound 91). heated to reflux for 10 days The reaction was cooled concentrated in vacuo distilled water