1-methylazepan-4-one

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 title compound was prepared by following general procedure 1. p-Tolyl hydrazine hydrochloride (15 g, 94.55 mmol) was taken into 7% H2SO4 in 1,4-dioxane (650 mL), 1-methylazepan-4-one.HCl (15.4 g, 94.55 mmol) was added and stirred at RT for 10 min. The reaction mixture was stirred at 80° C. for 14 h. After completion of the reaction, reaction mass was slowly basified with 50% NaOH solution, extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and evaporated to dryness and purified by column chromatography (silica gel 100-200 mesh; eluent: 10% methanol-DCM) to afford 3,9-dimethyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (5 g). The title compound was prepared The reaction mixture was stirred at 80° C. for 14 h After completion of the reaction, reaction mass extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate evaporated to dryness purified by column chromatography (silica gel 100-200 mesh; eluent: 10% methanol-DCM)

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

実験手順: The title compound was prepared by following general procedure 1. p-Tolyl hydrazine hydrochloride (15 g, 94.55 mmol) was taken into 7% H2SO4 in 1,4-dioxane (650 mL), 1-methylazepan-4-one.HCl (15.4 g, 94.55 mmol) was added and stirred at RT for 10 min. The reaction mixture was stirred at 80° C. for 14 h. After completion of the reaction, reaction mass was slowly basified with 50% NaOH solution, extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and evaporated to dryness and purified by column chromatography (silica gel 100-200 mesh; eluent: 10% methanol-DCM) to afford 3,9-dimethyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (5 g). The title compound was prepared The reaction mixture was stirred at 80° C. for 14 h After completion of the reaction, reaction mass extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate evaporated to dryness purified by column chromatography (silica gel 100-200 mesh; eluent: 10% methanol-DCM)

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: Reaction of 2,3,4,5,6,7-hexahydro-1-methylazepin-4-one and 2-(2-bromophenyl)-4,4-dimethyl-2-oxazoline by the method described in Example 1c provides 4-[2-(4,4-dimethyl-2-oxazolin-2-yl)phenyl]-2,3,4,5,6,7-hexahydro-4-hydroxy-1-methylazepine.

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

実験手順: N-methylazepan-4-one.HCl (50 mg, 0.30 mmol) and 4-nitrobenzaldehyde were dissolved in acetic acid (5 mL) and stirred for 10 min, then conc. H2SO4 (50 μL) was added slowly and the mixture was stirred at rt overnight. More concentrated H2SO4 (100 μL) was added and stirring was continued at rt for 6 h. Additional 500 μL of concentrated H2SO4 was added and the reaction stirred overnight. A further 350 μL of conc. H2SO4 was added and stirring continued for additional 5 h, during which period further H2SO4 was added in two portions (500 μL and 250 μL). Then water (3× reaction volume) was added and the mixture was stirred until rt was reached. The reaction mixture was extracted with ethyl acetate (3× reaction volume). The phases were separated and the organic phase concentrated to yield a dark yellow viscous oil. The crude product was purified by preparative HPLC, (XBridge column; eluents 50 mM ammonium carbonate buffer at pH 10 and methanol) giving the title product as a yellow solid (26.3 mg). LCMS System A: Rt 1.87 m/z [M+H]+ 394.1, System B: Rt 2.57. the mixture was stirred at rt overnight stirring was continued at rt for 6 h the reaction stirred overnight stirring was added in two portions (500 μL and 250 μL) the mixture was stirred until rt The reaction mixture was extracted with ethyl acetate (3× reaction volume) The phases were separated the organic phase concentrated to yield a dark yellow viscous oil The crude product was purified by preparative HPLC, (XBridge column; eluents 50 mM ammonium carbonate buffer at pH 10 and methanol)

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

実験手順: The title compound is prepared from 5-chloro-2-(piperidin-4-ylcarbonylamino)-N-(5-chloropyridin-2-yl)-benzamide and 1-methyl-hexahydro-4H-azepin-4-one by reductive alkylation using NaCNBH3 and 5%-acetic acid in methanol, for example using a procedure similar to that of Example 25-F.

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

実験手順: Reaction of 2,3,4,5,6,7-hexahydro-1-methylazepin-4-one and 2-(2-bromophenyl)-4,4-dimethyl-2-oxazoline by the method described in Example 1c provides 4-[2-(4,4-dimethyl-2-oxazolin-2-yl)phenyl]-2,3,4,5,6,7-hexahydro-4-hydroxy-1-methylazepine.

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

実験手順: The title compound was prepared by following general procedure 1. p-Tolyl hydrazine hydrochloride (15 g, 94.55 mmol) was taken into 7% H2SO4 in 1,4-dioxane (650 mL), 1-methylazepan-4-one.HCl (15.4 g, 94.55 mmol) was added and stirred at RT for 10 min. The reaction mixture was stirred at 80° C. for 14 h. After completion of the reaction, reaction mass was slowly basified with 50% NaOH solution, extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and evaporated to dryness and purified by column chromatography (silica gel 100-200 mesh; eluent: 10% methanol-DCM) to afford 3,9-dimethyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (5 g). The title compound was prepared The reaction mixture was stirred at 80° C. for 14 h After completion of the reaction, reaction mass extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate evaporated to dryness purified by column chromatography (silica gel 100-200 mesh; eluent: 10% methanol-DCM)