bis(diethoxyphosphoryl)methanamine

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:

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:

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: To a solution of tetraethyl (aminomethylene)bis-(phosphonate) (661 mg) in pyridine (2 ml) were added benzenesulfonyl chloride (0.35 ml) and then 4-(dimethylamino)pyridine (50 mg) at ambient temperature with stirring. After stirring for 4 hours at the same temperature, the reaction mixture was diluted with ethyl acetate (20 ml). The mixture was washed with 1N hydrochloric acid four times, water and saturated aqueous hydrogen bicarbonate solution successively. The organic layer was dried over magnesium sulfate and evaporated under reduced pressure. The residue was subjected to column chromatography on silica gel (20 g) eluted with a mixture of chloroform and methanol (20:1 V/V) to give tetraethyl (phenylsulfonylaminomethylene)bis(phosphonate) as a yellow syrup (364 mg). The mixture was washed with 1N hydrochloric acid four times, water and saturated aqueous hydrogen bicarbonate solution successively The organic layer was dried over magnesium sulfate evaporated under reduced pressure eluted with a mixture of chloroform and methanol (20:1 V/V)

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

実験手順: To a solution of 2-[1-(tert-butoxycarbonyl)-imidazol-4-yl]acetic acid (45 mg) and tetraethyl (aminomethylene)bis(phosphonate) (91 mg) in N,N-dimethylformamide (1 ml) was added N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (42 mg) with stirring on ice-sodium chloride bath under nitrogen atmosphere. After stirring for 36 hours at 5° C., the mixture was diluted with chloroform (10 ml) and washed with cold 1N aqueous solution of citric acid (10 ml). The aqueous layer was extracted with chloroform (10 ml) twice and the combined organic layers were dried over sodium sulfate and evaporated in vacuo. The residue was dissolved in ethyl acetate (10 ml) and the solution was washed with water (10 ml), dried over sodium sulfate and evaporated in vacuo to give a colorless syrup of tetraethyl [[2-{1-(tert-butoxycarbonyl)-imidazol-4-yl}acetamido]methylene]bis(phosphonate) (67 mg). After stirring for 36 hours at 5° C. washed with cold 1N aqueous solution of citric acid (10 ml) The aqueous layer was extracted with chloroform (10 ml) twice the combined organic layers were dried over sodium sulfate evaporated in vacuo The residue was dissolved in ethyl acetate (10 ml) the solution was washed with water (10 ml) dried over sodium sulfate evaporated in vacuo

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

実験手順: To a solution of 2-[1-(tert-butoxycarbonyl)-imidazol-4-yl]acetic acid (45 mg) and tetraethyl (aminomethylene)bis(phosphonate) (91 mg) in N,N-dimethylformamide (1 ml) was added N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (42 mg) with stirring on ice-sodium chloride bath under nitrogen atmosphere. After stirring for 36 hours at 5° C., the mixture was diluted with chloroform (10 ml) and washed with cold 1N aqueous solution of citric acid (10 ml). The aqueous layer was extracted with chloroform (10 ml) twice and the combined organic layers were dried over sodium sulfate and evaporated in vacuo. The residue was dissolved in ethyl acetate (10 ml) and the solution was washed with water (10 ml), dried over sodium sulfate and evaporated in vacuo to give a colorless syrup of tetraethyl [[2-{1-(tert-butoxycarbonyl)-imidazol-4-yl}acetamido]methylene]bis(phosphonate) (67 mg). After stirring for 36 hours at 5° C. washed with cold 1N aqueous solution of citric acid (10 ml) The aqueous layer was extracted with chloroform (10 ml) twice the combined organic layers were dried over sodium sulfate evaporated in vacuo The residue was dissolved in ethyl acetate (10 ml) the solution was washed with water (10 ml) dried over sodium sulfate evaporated in vacuo

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

実験手順: To a solution of 2-benzo[b]thiophenecarbonyl chloride prepared from 2-benzo[b]thiophenecarboxylic acid (356 mg) and oxalyl chloride (0.35 ml) in methylene chloride (2 ml) was added dropwise a mixture of tetraethyl (aminomethylene)bis(phosphonate) (606 mg), pyridine (316 mg) and trace amounts of 4-(dimethylamino)pyridine in methylene at 5° C. The mixture was stirred for 2 chloride (8 ml) hours at ambient temperature followed by the addition of ethyl acetate. The mixture was washed with water, 1N hydrochloric acid, saturated aqueous solution of sodium bicarbonate and brine successively. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was treated with diisopropyl ether to give tetraethyl [(2-benzo[b]thiophenecarboxamido)-methylene]bis(phosphonate) (790 mg) as a white powder which was recrystallized from a mixture of ethyl acetate and n-hexane. was added dropwise at 5° C The mixture was washed with water, 1N hydrochloric acid, saturated aqueous solution of sodium bicarbonate and brine successively The organic layer was dried over magnesium sulfate concentrated under reduced pressure The residue was treated with diisopropyl ether

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

実験手順: 17.1 g (35.4 mmol) of tetraethyl N,N-dibenzyl-aminomethane-1,1-bisphosphonate are dissolved in 170 ml of ethanol and 3.4 g of 5% strength Pd/C are added. Hydrogenation is carried out at normal pressure. After absorption of 100 ml of hydrogen, a further 3.4 g of 5% strength Pd/C are added and the hydrogenation is completed at normal pressure and room temperature (reaction time about 16 hours). The catalyst is then filtered off with suction. After removal of the solvent, 10.9 g of crude product are obtained. This is purified on a silica gel column using ethanol as the eluent. After absorption of 100 ml of hydrogen a further 3.4 g of 5% strength Pd/C are added the hydrogenation is completed at normal pressure and room temperature (reaction time about 16 hours) The catalyst is then filtered off with suction After removal of the solvent, 10.9 g of crude product are obtained This is purified on a silica gel column