4-[benzyl(methyl)amino]cyclohexan-1-one

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

実験手順: n-BuLi (3 ml, 5.98 mmol, 1.2 eq., 2 M solution in hexane) was added at −78° C. to a solution of 4-bromo-N,N-dimethylpyridin-2-amine (978 mg, 5.23 mmol, 1.05 eq.) in diethyl ether (15 ml) and the mixture was stirred for 45 minutes. A solution of 4-(benzyl(methyl)amino)cyclo-hexanone (stage 3, AMN-50) (1.08 g, 4.9, 8 mmol 1.0 eq.) in diethyl ether (10 ml) was added dropwise thereto at the same temperature. The reaction mixture was stirred for 16 hours at RT and was then hydrolyzed with sat. ammonium chloride solution (30 ml) and extracted with ethyl acetate (3×60 ml). The combined org. phases were washed with sat. NaCl solution (100 ml), dried over sodium sulfate, concentrated and purified by column chromatography (silica gel, 2,5% MeOH in DCM). Yield: 71% (1.20 g, 3.54 mmol) The reaction mixture was stirred for 16 hours at RT hydrolyzed with sat. ammonium chloride solution (30 ml) and extracted with ethyl acetate (3×60 ml) phases were washed with sat. NaCl solution (100 ml) dried over sodium sulfate concentrated purified by column chromatography (silica gel, 2,5% MeOH in DCM)

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

実験手順: 4-(Benzyl(methyl)amino)cyclohexanone (680 mg, 3.133 mmol, 1.0 eq.) and 1,2,3,4-tetrahydro-2,6-naphthyridine dihydrochloride (713 mg, 3.44 mmol, 1.1 eq.) were dissolved in MeOH (20 ml) and the mixture was stirred for 5 hours at RT. Then the solution was cooled to 0° C., NaCNBH3 (393 mg, 3.26 mmol, 2.0 eq.) was added and the mixture was stirred for 16 hours at RT. The reaction solution was concentrated to dryness under reduced pressure and purified by column chromatography (Alox, 1.2% MeOH in DCM). Yield: 38% (400 mg, 1.194 mmol) Then the solution was cooled to 0° C. the mixture was stirred for 16 hours at RT The reaction solution was concentrated to dryness under reduced pressure purified by column chromatography (Alox, 1.2% MeOH in DCM)

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

実験手順: N-Benzyl-N-methyl-1,4-dioxaspiro[4.5]decan-8-amine (1.0 g, 3.83 mmol, 1.0 eq.) was dissolved in MeOH (12 ml); 6 M HCl solution (12 ml) was added at 0° C., and stirring was carried out for 16 hours at RT. After monitoring by TLC, the solvent was removed under reduced pressure and the residue was taken up in water (50 ml), adjusted to pH 8-9 with NaCHO3 (solid) and extracted with DCM (2×50 ml). The combined org. phases were washed with water and sat. NaCl solution (in each case 50 ml), dried over sodium sulfate and concentrated under reduced pressure and dried. The crude product was used in the next stage without being purified further. Yield: 74% (620 mg, 2.857 mmol) the solvent was removed under reduced pressure extracted with DCM (2×50 ml) phases were washed with water and sat. NaCl solution (in each case 50 ml), dried over sodium sulfate concentrated under reduced pressure dried without being purified further