1-piperidin-4-ylimidazolidin-2-one

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: The mixture of 4.0 g of 2-(2-tosyloxyethyl)-6,7-dichloro-1,4-benzodioxan, 1.69 g of 1-(4-piperidyl)-2-imidazolidinone, 10 g of ahydrous sodium carbonate and 100 ml of 4-methyl-2-pentanone is stirred and refluxed for 2 days. It is filtered, evaporated and the residue recrystallized from acetone, to yield the 1-[1-[2-(6,7-dichloro-1,4-benzodioxan-2-yl)-ethyl]-4-piperidyl]-2-imidazolidinone melting at 165°. refluxed for 2 days It is filtered evaporated the residue recrystallized from acetone

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

実験手順: The mixture of 4.0 g of 2-(2-tosyloxyethyl)-6,7-dichloro-1,4-benzodioxan, 1.69 g of 1-(4-piperidyl)-2-imidazolidinone, 10 g of ahydrous sodium carbonate and 100 ml of 4-methyl-2-pentanone is stirred and refluxed for 2 days. It is filtered, evaporated and the residue recrystallized from acetone, to yield the 1-[1-[2-(6,7-dichloro-1,4-benzodioxan-2-yl)-ethyl]-4-piperidyl]-2-imidazolidinone melting at 165°. refluxed for 2 days It is filtered evaporated the residue recrystallized from acetone

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

実験手順: The mixture of 4.9 g of 2-(2-tosyloxyethyl)-1,4-benzodioxan, 2.54 g of 1-(4-piperidyl)-2-imidazolidinone, 5 g of anhydrous sodium carbonate and 100 ml of 4-methyl-2-pentanone is stirred and refluxed for 3 days. It is filtered, evaporated and the residue recrystallized from isopropanol, to yield the 1-[1-[2-(1,4-benzodioxan-2-yl)-ethyl]-4-piperidyl]-2-imidazolidinone of the formula ##STR9## melting at 125°. refluxed for 3 days It is filtered evaporated the residue recrystallized from isopropanol

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

実験手順: To a solution of 4.5 g of 4-formyl-4-methyl-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepine in 50 ml of methanol is added 3.6 ml of 5.5N methanolic HCl and 3.4 g of 1,3,4,5-tetrahydro-1-(4-piperidinyl)-2H-imidazol-2-one followed by 900 mg of sodium cyanoborohydride. The reaction mixture is allowed to stir at room temperature for 8 days. 2 ml of conc. HCl is added to the reaction mixture and the solvent is removed by evaporation under reduced pressure. The residue is dissolved in 150 ml water and washed with 150 ml of 1:1 ethyl acetate-ether mixture. The aqueous phase is separated, basified with dilute sodium hydroxide to pH 9 and extracted with 2×150 ml of ethyl acetate. The combined ethyl acetate extracts are dried over anhydrous MgSO4, filtered, and the solvent is removed by evaporation under reduced pressure to yield 1,3,4,5-tetrahydro-1-{1-[(4-methyl-4H,6H-pyrrolo[ 1,2-a][4,1]benzoxazepin-4-yl)-methyl]-4-piperidinyl}-2H-imidazol-2-one which is characterized as its maleate salt, m.p. 197°-199°. the solvent is removed by evaporation under reduced pressure The residue is dissolved in 150 ml water washed with 150 ml of 1:1 ethyl acetate-ether mixture The aqueous phase is separated extracted with 2×150 ml of ethyl acetate The combined ethyl acetate extracts are dried over anhydrous MgSO4 filtered the solvent is removed by evaporation under reduced pressure

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

実験手順: To a solution of 4.5 g of 4-formyl-4-methyl-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepine in 50 ml of methanol is added 3.6 ml of 5.5N methanolic HCl and 3.4 g of 1,3,4,5-tetrahydro-1-(4-piperidinyl)-2H-imidazol-2-one followed by 900 mg of sodium cyanoborohydride. The reaction mixture is allowed to stir at room temperature for 8 days. 2 ml of conc. HCl is added to the reaction mixture and the solvent is removed by evaporation under reduced pressure. The residue is dissolved in 150 ml water and washed with 150 ml of 1:1 ethyl acetate-ether mixture. The aqueous phase is separated, basified with dilute sodium hydroxide to pH 9 and extracted with 2×150 ml of ethyl acetate. The combined ethyl acetate extracts are dried over anhydrous MgSO4, filtered, and the solvent is removed by evaporation under reduced pressure to yield 1,3,4,5-tetrahydro-1-{1-[(4-methyl-4H,6H-pyrrolo[ 1,2-a][4,1]benzoxazepin-4-yl)-methyl]-4-piperidinyl}-2H-imidazol-2-one which is characterized as its maleate salt, m.p. 197°-199°. the solvent is removed by evaporation under reduced pressure The residue is dissolved in 150 ml water washed with 150 ml of 1:1 ethyl acetate-ether mixture The aqueous phase is separated extracted with 2×150 ml of ethyl acetate The combined ethyl acetate extracts are dried over anhydrous MgSO4 filtered the solvent is removed by evaporation under reduced pressure

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

実験手順: 4.8 g of 2-benzyloxy-3-(2,3-epoxypropoxy)-pyridine and 3.0 g of 1-(4-piperidyl)-imidazolidin-2-one are dissolved in 50 ml of isopropanol and the solution is stirred for 15-18 hours at 20-30°. The crystals which have precipitated out are filtered off with suction and washed with ether and yield 1-{1-[2-hydroxy-3-(2-benzyloxy-3-pyridyloxy)-propyl]-4-piperidyl}-imidazolidin-2-one with a melting point of 145°-147°. The crystals which have precipitated out are filtered off with suction washed with ether

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

実験手順: 4.8 g of 2-benzyloxy-3-(2,3-epoxypropoxy)-pyridine and 3.0 g of 1-(4-piperidyl)-imidazolidin-2-one are dissolved in 50 ml of isopropanol and the solution is stirred for 15-18 hours at 20-30°. The crystals which have precipitated out are filtered off with suction and washed with ether and yield 1-{1-[2-hydroxy-3-(2-benzyloxy-3-pyridyloxy)-propyl]-4-piperidyl}-imidazolidin-2-one with a melting point of 145°-147°. The crystals which have precipitated out are filtered off with suction washed with ether

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

実験手順: 1.1 g of 2-chloro-3-(2,3-epoxy-propoxy)-6-methylpyridine and 0.76 g of 1-(4-piperidyl)-imidazolidin-2-one are refluxed in 40 ml of isopropanol for 1 hour. Evaporating off the solvent and recrystallising the residue from the isopropanol/ether yields 1-{1-[2-hydroxy-3-(2-chloro-6-methyl-3-pyridyloxy)-propyl]-4-piperidyl}-imidazolidin-2-one with a melting point of 175°-180°. Evaporating off the solvent recrystallising the residue from the isopropanol/ether

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

実験手順: 1.1 g of 2-chloro-3-(2,3-epoxy-propoxy)-6-methylpyridine and 0.76 g of 1-(4-piperidyl)-imidazolidin-2-one are refluxed in 40 ml of isopropanol for 1 hour. Evaporating off the solvent and recrystallising the residue from the isopropanol/ether yields 1-{1-[2-hydroxy-3-(2-chloro-6-methyl-3-pyridyloxy)-propyl]-4-piperidyl}-imidazolidin-2-one with a melting point of 175°-180°. Evaporating off the solvent recrystallising the residue from the isopropanol/ether

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

実験手順: A mixture of 46.0 g of 3-(2,3-epoxy-propoxy)-2-nitropyridine and 35.0 g of 1-(4-piperidyl)-imidazolidin-2-one in 500 ml of isopropanol is refluxed for 2 hours. Working up analogously to Example 1 using methylene chloride as the extracting agent yields crude 1-{1-[2-hydroxy-3-(2-nitro-3-pyridyloxy)-propyl]-4-piperidyl}-imidazolidin-2-one, which after recrystallisation from isopropanol melts at 154°-158°. is refluxed for 2 hours