N,N-dimethyl-1-piperidin-4-ylmethanamine;dihydrochloride

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

実験手順: To a solution of phenyl N-[4-(3-fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-phenoxycarbonylcarbamate (50.0 mg) in N,N-dimethylformamide (1.0 ml) were added 4-(dimethylaminomethyl)piperidine dihydrochloride (67.0 mg), triethylamine (0.0523 ml) and water (0.050 ml), followed by stirring at room temperature for 10 hr. To the reaction mixture were added triethylamine (0.0523 ml) and water (0.050 ml), followed by further stirring at room temperature for 24 hr. The reaction mixture was partitioned between ethyl acetate and a 1N aqueous solution of sodium hydroxide. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed, and the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate, then ethyl acetate:methanol=20:1). Fractions containing the target compound were concentrated. To the residue was added hexane, and the precipitate was collected by filtration. This was washed with hexane and dried under aeration to provide the titled compound as white powder (22.4 mg, 50.4%). by further stirring at room temperature for 24 hr The reaction mixture was partitioned between ethyl acetate The organic layer was washed with brine dried over anhydrous sodium sulfate The solvent was removed the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate Fractions containing the target compound were concentrated To the residue was added hexane the precipitate was collected by filtration This was washed with hexane dried under aeration

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

実験手順: To a solution of phenyl N-[4-(3-fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-phenoxycarbonylcarbamate (50.0 mg) in N,N-dimethylformamide (1.0 ml) were added 4-(dimethylaminomethyl)piperidine dihydrochloride (67.0 mg), triethylamine (0.0523 ml) and water (0.050 ml), followed by stirring at room temperature for 10 hr. To the reaction mixture were added triethylamine (0.0523 ml) and water (0.050 ml), followed by further stirring at room temperature for 24 hr. The reaction mixture was partitioned between ethyl acetate and a 1N aqueous solution of sodium hydroxide. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed, and the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate, then ethyl acetate:methanol=20:1). Fractions containing the target compound were concentrated. To the residue was added hexane, and the precipitate was collected by filtration. This was washed with hexane and dried under aeration to provide the titled compound as white powder (22.4 mg, 50.4%). by further stirring at room temperature for 24 hr The reaction mixture was partitioned between ethyl acetate The organic layer was washed with brine dried over anhydrous sodium sulfate The solvent was removed the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate Fractions containing the target compound were concentrated To the residue was added hexane the precipitate was collected by filtration This was washed with hexane dried under aeration