1,2,3,4-tetrahydro-1-benzazepin-5-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:

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 1.67 g portion of 2'-methoxybiphen-4-ylcarboxylic acid was dissolved in 17 ml of dichloromethane, 0.95 ml of oxalyl chloride and a catalytically effective amount of dimethylformamide were added to the resulting solution with cooling on an ice bath and then the resulting mixture was warmed up to room temperature. When completion of foaming was confirmed, the reaction solution was concentrated under a reduced pressure and subjected to azeotropic treatment with toluene twice. The thus obtained residue was dissolved in 8.4 ml of dichloromethane and, with cooling on an ice bath, the resulting solution was dropwise added to a solution obtained by dissolving 1.0 g of 5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine and 1.53 ml of triethylamine in 10 ml of dichloromethane. The reaction solution was warmed up to room temperature and the stirring was continued for 1 hour. The resulting reaction solution was mixed with water and subjected to phase separation to separate dichloromethane layer which was subsequently washed with 0.5N hydrochloric acid and a saturated sodium bicarbonate aqueous solution and dried over anhydrous magnesium sulfate. After removing the solvent by distillation, the thus obtained residue was crystallized from toluene to obtain 1.65 g of 1-(2'-methoxybiphen-4-ylcarbonyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine as crude crystals. with cooling on an ice bath the reaction solution was concentrated under a reduced pressure The thus obtained residue was dissolved in 8.4 ml of dichloromethane with cooling on an ice bath the resulting solution was dropwise added to a solution obtained The reaction solution was warmed up to room temperature The resulting reaction solution subjected to phase separation to separate dichloromethane layer which was subsequently washed with 0.5N hydrochloric acid a saturated sodium bicarbonate aqueous solution and dried over anhydrous magnesium sulfate After removing the solvent by distillation the thus obtained residue was crystallized from toluene

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 mixture of 1,2,3,4-tetrahydro-1-benzazepin-5-one (500 mg, 2.530 mmol), O-methyl hydroxylamine hydrochloride (211 mg, 2.530 mmol), sodium acetate (208 mg, 2.530 mmol) and sodium carbonate (536 mg, 5.060 mmol) in ethanol was refluxed for 3 hours. The resulting mixture was concentrated in vacuo to remove ethanol and to the residue was added water (15 mL). The residue in water was extracted with dichloromethane (15 mL×3). The organic layers were combined, dried over sodium sulfate, and concentrated in vacuo to afford 326 mg of the desired product (yield was 67%). was refluxed for 3 hours The resulting mixture was concentrated in vacuo to remove ethanol to the residue was added water (15 mL) The residue in water was extracted with dichloromethane (15 mL×3) dried over sodium sulfate concentrated in vacuo

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

実験手順: A 1.67 g portion of 2'-methoxybiphen-4-ylcarboxylic acid was dissolved in 17 ml of dichloromethane, 0.95 ml of oxalyl chloride and a catalytically effective amount of dimethylformamide were added to the resulting solution with cooling on an ice bath and then the resulting mixture was warmed up to room temperature. When completion of foaming was confirmed, the reaction solution was concentrated under a reduced pressure and subjected to azeotropic treatment with toluene twice. The thus obtained residue was dissolved in 8.4 ml of dichloromethane and, with cooling on an ice bath, the resulting solution was dropwise added to a solution obtained by dissolving 1.0 g of 5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine and 1.53 ml of triethylamine in 10 ml of dichloromethane. The reaction solution was warmed up to room temperature and the stirring was continued for 1 hour. The resulting reaction solution was mixed with water and subjected to phase separation to separate dichloromethane layer which was subsequently washed with 0.5N hydrochloric acid and a saturated sodium bicarbonate aqueous solution and dried over anhydrous magnesium sulfate. After removing the solvent by distillation, the thus obtained residue was crystallized from toluene to obtain 1.65 g of 1-(2'-methoxybiphen-4-ylcarbonyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine as crude crystals. with cooling on an ice bath the reaction solution was concentrated under a reduced pressure The thus obtained residue was dissolved in 8.4 ml of dichloromethane with cooling on an ice bath the resulting solution was dropwise added to a solution obtained The reaction solution was warmed up to room temperature The resulting reaction solution subjected to phase separation to separate dichloromethane layer which was subsequently washed with 0.5N hydrochloric acid a saturated sodium bicarbonate aqueous solution and dried over anhydrous magnesium sulfate After removing the solvent by distillation the thus obtained residue was crystallized from toluene

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

実験手順: Cyclopropanecarboxylic acid 4-(1-benzyl-2-methyl-4,5-dihydro-1H-1,3,6-triaza-benzo[e]azulene-6-carbonyl)-2-methyl-benzylamide from Example E123.1 (155 mg, 0.31 mmol) was dissolved in absolute ethanol (10 ml) and placed under an inert atmosphere. 10% Palladium on car-bon (155 mg) and cyclohexene (0.311 ml, 3.1 mmol) were added and the mixture was heated at 60° C. for 18 h. The catalyst was filtered off through Celite® filter agent and the filtrate was concentrated in vacuo. The residue was purified by preparative HPLC (eluant; 0.5% 35% ammonia:9.5% methanol:90% dichloromethane) to give a white solid identified as the title compound (67 mg, 53%). The catalyst was filtered off through Celite® filter agent the filtrate was concentrated in vacuo The residue was purified by preparative HPLC (eluant; 0.5% 35% ammonia:9.5% methanol:90% dichloromethane) to give a white solid

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

実験手順: [2-Chloro-4-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzyl]-carbamic acid tert-butyl ester from Example E106.1 (570 mg, 1.13 mmol) was reacted with 4N HCl/dioxan using an analogous procedure to that described for Example E4.2 to yield the title compound (490 mg, 100%).