4-[chloro(morpholin-4-yl)phosphoryl]morpholine

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: A solution of 1.075 g of 7-chloro-5-phenyl-1,3-dihydro-2H-1-benzazepin-2-one in 20 ml of dry tetrahydrofuran is treated with 0.23 g of sodium hydride (50% dispersion in mineral oil) and stirred at 60° for 1 hour. The mixture is then cooled to room temperature, treated with 1.53 g of bis-(4-morpholinyl)phosphinic acid chloride and stirred at this temperature for a further 2 hours. A solution of 0.593 g of acetic acid hydrazide in 50 ml of n-butanol is subsequently added thereto, the mixture is heated to boiling under reflux for 1 hour and then evaporated in vacuo. The residue is partitioned between water and methylene chloride. The methylene chloride solution is evaporated and the residue is chromatographed on 100 g of aluminium oxide (activity grade III). Various impurities and starting material are eluted successively with benzene and ethyl acetate/hexane (1:1). After elution with chloroform/ethanol (96:4) and recrystallization of the crude product from ethyl acetate/benzene/n-hexane, there is obtained 8-chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1]benzazepine of melting point 235°. stirred at this temperature for a further 2 hours the mixture is heated under reflux for 1 hour evaporated in vacuo The residue is partitioned between water and methylene chloride The methylene chloride solution is evaporated the residue is chromatographed on 100 g of aluminium oxide (activity grade III) are eluted successively with benzene and ethyl acetate/hexane (1:1) After elution with chloroform/ethanol (96:4) and recrystallization of the crude product from ethyl acetate/benzene/n-hexane

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

実験手順: To a stirred solution of 915 mg (3.0 mmoles) of 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one in 10 ml of dry tetrahydrofuran was added 173 mg of a 50% dispersion as sodium hydride in oil (3.6 mmoles of hydride). The mixture was stirred at room temperature approximately 1 hr until hydrogen evolution stopped. Dimorpholinophosphinic chloride (1.5 g; 6.0 mmoles) was added and the resulting mixture was stirred at room temperature for 2 hrs. Insoluble salts were removed by filtration. Tetrahydrofuran was evaporated. The residue was crystallized from ethyl acetate to give colorless needles, mp 185°-187°. Insoluble salts were removed by filtration Tetrahydrofuran was evaporated The residue was crystallized from ethyl acetate to give colorless needles, mp 185°-187°

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

実験手順: To a stirred solution of 915 mg (3.0 mmoles) of 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one in 10 ml of dry tetrahydrofuran was added 173 mg of a 50% dispersion as sodium hydride in oil (3.6 mmoles of hydride). The mixture was stirred at room temperature approximately 1 hr until hydrogen evolution stopped. Dimorpholinophosphinic chloride (1.5 g; 6.0 mmoles) was added and the resulting mixture was stirred at room temperature for 2 hrs. Insoluble salts were removed by filtration. Tetrahydrofuran was evaporated. The residue was crystallized from ethyl acetate to give colorless needles, mp 185°-187°. Insoluble salts were removed by filtration Tetrahydrofuran was evaporated The residue was crystallized from ethyl acetate to give colorless needles, mp 185°-187°

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

実験手順: To a stirred solution of 4.74 g (15 mmoles) of 5-(2-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one in 80 ml of dry tetrahydrofuran at room temperature was added 875 mg of a 50% dispersion of sodium hydride in oil (18 mmoles of hydride). The mixtute was stirred at room temperature for 1 hr until hydrogen evolution stopped. Dimorpholinophosphinic chloride (7.5 g, 30 mmoles) was added and the resulting mixture was stirred at room temperature for 3 hrs. Solids (mixture of product and salt) were collected and partitioned between water and methylene chloride. The methylene chloride layer was dried and evaporated. Crystallization of the residue from methylene chloride ether gave colorless needles, mp 214°-216°. Solids (mixture of product and salt) were collected partitioned between water and methylene chloride The methylene chloride layer was dried evaporated Crystallization of the residue from methylene chloride ether gave colorless needles, mp 214°-216°

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

実験手順: To a solution of 610 mg. (2 mmoles) of 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one in 10 ml. of dry tetrahydrofuran at room temperature was added 115 mg. of a 50% dispersion of sodium hydride in oil (2.4 mmoles of hydride). The mixture was warmed gently on the steam bath for approximately 1 hour until hydrogen evolution stopped. Dimorpholinophosphinic chloride (764 mg., 3.0 mmoles) was added and the resulting mixture was stirred at room temperature for 2 hours. To this mixture was then added a solution of 296 mg. (4 mmoles) of acethydrazide in 5 ml. of dry tetrahydrofuran and stirring was continued for 15 minutes at room temperature. Solvents were evaporated and the residue was dissolved in 20 ml. of butanol and heated to reflux for 2 hours. Butanol was evaporated. The residue was partitioned between methylene chloride and water. The methylene chloride layer was dried and evaporated. Crystallization of the residue from isopropanol-ether-petroleum ether yielded, in two crops, final product having a m.p. of 225°-227°. To this mixture was then added a solution of 296 mg was continued for 15 minutes at room temperature Solvents were evaporated the residue was dissolved in 20 ml of butanol and heated to reflux for 2 hours Butanol was evaporated The residue was partitioned between methylene chloride and water The methylene chloride layer was dried evaporated Crystallization of the residue from isopropanol-ether-petroleum ether

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

実験手順: A solution of 1.075 g of 7-chloro-5-phenyl-1,3-dihydro-2H-1-benzazepin-2-one in 20 ml of dry tetrahydrofuran is treated with 0.23 g of sodium hydride (50% dispersion in mineral oil) and stirred at 60° for 1 hour. The mixture is then cooled to room temperature, treated with 1.53 g of bis-(4-morpholinyl)phosphinic acid chloride and stirred at this temperature for a further 2 hours. A solution of 0.593 g of acetic acid hydrazide in 50 ml of n-butanol is subsequently added thereto, the mixture is heated to boiling under reflux for 1 hour and then evaporated in vacuo. The residue is partitioned between water and methylene chloride. The methylene chloride solution is evaporated and the residue is chromatographed on 100 g of aluminium oxide (activity grade III). Various impurities and starting material are eluted successively with benzene and ethyl acetate/hexane (1:1). After elution with chloroform/ethanol (96:4) and recrystallization of the crude product from ethyl acetate/benzene/n-hexane, there is obtained 8-chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1]benzazepine of melting point 235°. stirred at this temperature for a further 2 hours the mixture is heated under reflux for 1 hour evaporated in vacuo The residue is partitioned between water and methylene chloride The methylene chloride solution is evaporated the residue is chromatographed on 100 g of aluminium oxide (activity grade III) are eluted successively with benzene and ethyl acetate/hexane (1:1) After elution with chloroform/ethanol (96:4) and recrystallization of the crude product from ethyl acetate/benzene/n-hexane

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

実験手順: A solution of 1.075 g of 7-chloro-5-phenyl-1,3-dihydro-2H-1-benzazepin-2-one in 20 ml of dry tetrahydrofuran is treated with 0.23 g of sodium hydride (50% dispersion in mineral oil) and stirred at 60° for 1 hour. The mixture is then cooled to room temperature, treated with 1.53 g of bis-(4-morpholinyl)phosphinic acid chloride and stirred at this temperature for a further 2 hours. A solution of 0.593 g of acetic acid hydrazide in 50 ml of n-butanol is subsequently added thereto, the mixture is heated to boiling under reflux for 1 hour and then evaporated in vacuo. The residue is partitioned between water and methylene chloride. The methylene chloride solution is evaporated and the residue is chromatographed on 100 g of aluminium oxide (activity grade III). Various impurities and starting material are eluted successively with benzene and ethyl acetate/hexane (1:1). After elution with chloroform/ethanol (96:4) and recrystallization of the crude product from ethyl acetate/benzene/n-hexane, there is obtained 8-chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1]benzazepine of melting point 235°. stirred at this temperature for a further 2 hours the mixture is heated under reflux for 1 hour evaporated in vacuo The residue is partitioned between water and methylene chloride The methylene chloride solution is evaporated the residue is chromatographed on 100 g of aluminium oxide (activity grade III) are eluted successively with benzene and ethyl acetate/hexane (1:1) After elution with chloroform/ethanol (96:4) and recrystallization of the crude product from ethyl acetate/benzene/n-hexane

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir: