1-benzylazepan-4-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 33% hydrobromic acid in conc. acetic acid and 1.97 g bromine was added to 5 g 1-benzyl-azepane-4-one in 15 mL conc. acetic acid. The reaction was stirred 2 h at RT and completely concentrated under reduced pressure. The residue was diluted with ethyl acetate and refluxed for 1 h and crystallized with ethyl acetate to give 4 g of the desired product. completely concentrated under reduced pressure The residue was diluted with ethyl acetate refluxed for 1 h crystallized with ethyl acetate

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6 mL benzyl bromide was added to 5 g azepane-4-one hydrochloride and 18.5 g potassium carbonate in 50 mL THF and 25 mL water. The mixture was stirred 5 h at 50° C., evaporated, diluted with water and extracted with ethyl acetate. The organic layer was evaporated. The residue was purified by chromatographie on silica gel (petrolether/ethyl acetate:8/2) to give 5 g of the desired product. Rf: 0.40 (hexane/ethyl acetate=1/1), (M+H)+=204 evaporated diluted with water extracted with ethyl acetate The organic layer was evaporated The residue was purified by chromatographie on silica gel (petrolether/ethyl acetate:8/2)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared from 1-benzyl-hexahydro-4-azepinone with ethyl formate and ethyl malonamate in the presence of sodium hydride.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7.2 g of 1-benzylazacycloheptan-4-one are added to a solution of 3.1 g of hydroxylamine hydrochloride and 2.9 g of sodium acetate in 30 ml of water at 60° C. After 2 hours, the mixture is cooled and made alkaline with 2N sodium hydroxide solution. The mixture is extracted four times with diethyl ether, the organic phases are washed with saturated sodium chloride solution and dried over magnesium sulphate, and the solvent is distilled off in a rotary evaporator. The residue is triturated with petroleum ether, filtered off with suction and employed without further purification. the mixture is cooled The mixture is extracted four times with diethyl ether the organic phases are washed with saturated sodium chloride solution dried over magnesium sulphate the solvent is distilled off in a rotary evaporator The residue is triturated with petroleum ether filtered off with suction employed without further purification

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of DIPA (3.1 mL) in THF (30 mL) was added dropwise a 2.6 M solution (8.6 mL) of n-butyl lithium in hexane at −70° C. After stirring at 0° C. for 40 minutes, EtOAc (2.3 mL) was added dropwise thereto at −70° C., followed by stirring for 5 minutes. A solution of 1-benzylazepan-4-one (3.6 g) in THF (10 mL) was added dropwise thereto, followed by stirring for 40 minutes. To the reaction mixture was added a saturated aqueous NH4Cl solution, followed by addition of water and extraction with EtOAc. The organic layer was washed with brine, dried over MgSO4, and then concentrated under reduced pressure. The residue was purified by medium-pressure preparative liquid chromatography (silica gel, YAMAZEN YFLC WPrep2XY, CHCl3:MeOH: aqueous ammonia) to obtain ethyl (1-benzyl-4-hydroxyazepan-4-yl)acetate (5.0 g) as a yellow oily substance. at −70° C. by stirring for 5 minutes by stirring for 40 minutes The organic layer was washed with brine dried over MgSO4 concentrated under reduced pressure The residue was purified by medium-pressure preparative liquid chromatography (silica gel, YAMAZEN YFLC WPrep2XY, CHCl3:MeOH: aqueous ammonia)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 33% hydrobromic acid in conc. acetic acid and 1.97 g bromine was added to 5 g 1-benzyl-azepane-4-one in 15 mL conc. acetic acid. The reaction was stirred 2 h at RT and completely concentrated under reduced pressure. The residue was diluted with ethyl acetate and refluxed for 1 h and crystallized with ethyl acetate to give 4 g of the desired product. completely concentrated under reduced pressure The residue was diluted with ethyl acetate refluxed for 1 h crystallized with ethyl acetate

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6 mL benzyl bromide was added to 5 g azepane-4-one hydrochloride and 18.5 g potassium carbonate in 50 mL THF and 25 mL water. The mixture was stirred 5 h at 50° C., evaporated, diluted with water and extracted with ethyl acetate. The organic layer was evaporated. The residue was purified by chromatographie on silica gel (petrolether/ethyl acetate:8/2) to give 5 g of the desired product. Rf: 0.40 (hexane/ethyl acetate=1/1), (M+H)+=204 evaporated diluted with water extracted with ethyl acetate The organic layer was evaporated The residue was purified by chromatographie on silica gel (petrolether/ethyl acetate:8/2)

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: n-Butyllithium (1.6M in hexanes, 0.164 mol) was added dropwise at −30° C. under N2 flow to a mixture of N-(1-methylethyl)-2-propanamine (0.164 mol) in THF (70 ml). The mixture was cooled to −70° C. A mixture of 1-methyl-1H-imidazo[4,5-b]pyridine (0.0751 mol) in THF (70 ml) was added dropwise. The mixture was stirred for 1 hour. A mixture of hexahydro-1-(phenylmethyl)-4H-azepin-4-one (0.0787 mol) in THF (60 ml) was added at −70° C. The mixture was stirred at −70° C. for 2 hours, brought to 0° C., poured out into water and NH4Cl and extracted with DCM and a small amount of methanol. The organic layer was separated, dried, filtered and evaporated to dryness. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 97/3/0.5). The desired fractions were collected and the solvent was evaporated, yielding 8.8 g of (±)-hexahydro-4-(1-methyl-1H-imidazo[4,5-b]pyridin-2-yl)-1-(phenylmethyl)-1H-azepin-4-ol (compound 152). was added dropwise was added at −70° C The mixture was stirred at −70° C. for 2 hours brought to 0° C. extracted with DCM The organic layer was separated dried filtered evaporated to dryness The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 97/3/0.5) The desired fractions were collected the solvent was evaporated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of hexahydro-1-(phenylmethyl)-4H-azepin-4-one (0.2 mol) and 4-toluene-sulfonylmethyl isocyanide (0.25 mol) in DMF (200 ml) was stirred at 0° C. A solution of potassium tert-butoxide (0.4 mol) in a mixture of 2-methyl-2-propanol (200 ml) and 1,2-dimethoxyethane (200 ml) was added dropwise at 0° C. The mixture was allowed to reach room temperature and stirring was continued for 1 hour. The mixture was stirred in water and this mixture was extracted with DCM. The separated organic layer was dried, filtered and the solvent was evaporated, yielding 48 g of (±)-hexahydro-1-(phenylmethyl)-1H-azepine-4-carbonitrile (intermediate 1). was added dropwise at 0° C to reach room temperature stirring this mixture was extracted with DCM The separated organic layer was dried filtered the solvent was evaporated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of hexahydro-1-(phenylmethyl)-4H-azepin-4-one (0.2 mol) and 4-toluene-sulfonylmethyl isocyanide (0.25 mol) in DMF (200 ml) was stirred at 0° C. A solution of potassium tert-butoxide (0.4 mol) in a mixture of 2-methyl-2-propanol (200 ml) and 1,2-dimethoxyethane (200 ml) was added dropwise at 0° C. The mixture was allowed to reach room temperature and stirring was continued for 1 hour. The mixture was stirred in water and this mixture was extracted with DCM. The separated organic layer was dried, filtered and the solvent was evaporated, yielding 48 g of (±)-hexahydro-1-(phenylmethyl)-1H-azepine-4-carbonitrile (intermediate 1). was added dropwise at 0° C to reach room temperature stirring this mixture was extracted with DCM The separated organic layer was dried filtered the solvent was evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 33% hydrobromic acid in conc. acetic acid and 1.97 g bromine was added to 5 g 1-benzyl-azepane-4-one in 15 mL conc. acetic acid. The reaction was stirred 2 h at RT and completely concentrated under reduced pressure. The residue was diluted with ethyl acetate and refluxed for 1 h and crystallized with ethyl acetate to give 4 g of the desired product. completely concentrated under reduced pressure The residue was diluted with ethyl acetate refluxed for 1 h crystallized with ethyl acetate