tert-butyl (2S)-2-(aminomethyl)piperidine-1-carboxylate

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

実験手順: (S)-2-Aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (1.36 g) and 3,4,5-trifluorobenzonitrile (1.00 g) were heated under argon in xylene (10 ml) containing diisopropylethylamine (3.3 ml) for 16 h. The reaction mixture was cooled and partitioned between ethyl acetate and water. The organic phase was washed with brine, dried and evaporated to give a solid which was triturated with pentane-ether to afford the title product (0.16 g) as an off white powder. Chromatography of the mother liquors on silica gel eluting with ethyl acetate-pentane mixtures afforded further title product (0.92 g). Mass Spectrum (API+): Found 252 (MH+-tBoc). C18H23F2N3O2 requires 351. The reaction mixture was cooled partitioned between ethyl acetate and water The organic phase was washed with brine dried evaporated to give a solid which was triturated with pentane-ether

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

実験手順: (S)-2-Aminomethyl-piperidine-1-carboxylic acid tert butyl ester (1 g), 5-bromo-2-chloropyrimidine (0.9 g) were combined in xylene (20 ml) containing potassium carbonate (1.29 g) and diisopropylethylamine (2.43 g) and warmed to reflux for 48 h. The mixture was cooled to room temperature, filtered and solvent removed at reduced pressure. The residue was column chromatographed (silica gel, pentane-25% ethyl acetate/pentane). The appropriate fractions were collected, solvent removed at reduced pressure to give the title compound (1.43 g) as a colourless gum warmed to reflux for 48 h filtered solvent removed at reduced pressure chromatographed (silica gel, pentane-25% ethyl acetate/pentane) The appropriate fractions were collected solvent removed at reduced pressure

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

実験手順: The title compound (0.24 g) was prepared from (S)-2-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (1.14 g) and 2-chloro-4-cyanopyridine (0.74 g) according to the method of D28.

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

実験手順: The title compound (0.66 g) was prepared from (S)-2-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (1.55 g) and 2-chloro-3-cyanopyridine (1.0 g) according to the method of D28.

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

実験手順: The title compound (1.54 g) was prepared from (S)-2-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (2.0 g) and 2-chloro-5-cyanopyridine (1.29 g) in the presence of diisopropylethylamine (1.21 g) according to the method of D28.

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

実験手順: The title compound (0.28 g) was prepared from (S)-2-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (0.35 g) and 2-chloro-1,8-naphthyridine (0.19 g) according to the method of D30.

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

実験手順: The title compound (0.48 g) was prepared from (S)-2-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (0.59 g) and 2-chloro-1,5-naphthyridine Rapoport, et al J. Org. Chem. (1971), 36(3), 450-4 (0.40 g) according to the method of D30.

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

実験手順: The title compound (0.6 g) was prepared from (S)-2-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (0.68 g) and 2-chloroquinazolin (0.53 g) according to the method of D30.

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (S)-2-Aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (0.607 g), and 2-chloro-6,7-difluoroquinoxaline McQuaid et. al. J. Med. Chem. (1992), 35(18), 3319-24 (0.569 g) were dissolved in dimethylformamide (1 ml) and heated to 90° C. for 5 days under an atmosphere of argon. After cooling, the reaction solution was partitioned between ethyl acetate and water. The organic layer was washed with water, saturated brine, dried and evaporated. The residue was chromatographed over silica gel, eluting with a gradient of 10 to 50% ethyl acetate in hexane. The title compound was obtained as a pale yellow solid (0.460 g), MH+ 379. After cooling the reaction solution was partitioned between ethyl acetate and water The organic layer was washed with water, saturated brine dried evaporated The residue was chromatographed over silica gel eluting with a gradient of 10 to 50% ethyl acetate in hexane

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (S)-2-Aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (1.14 g), and 2-chloro-6,7-difluoro-3-methylquinoxaline Teng et al PCT Int. Appl (2000), WO00/42026A1 20000720 (1.14 g) were dissolved in DMF (2 ml) and heated to 90° C. for 3 days under an atmosphere of argon. After cooling, the reaction solution was partitioned between ethyl acetate and water. The organic layer was washed with water, saturated brine, dried and evaporated. The residue was chromatographed over silica gel, eluting with a gradient of 10 to 50% ethyl acetate in hexane. The title compound was obtained as a pink foam (0.524 g), MH+ 393. After cooling the reaction solution was partitioned between ethyl acetate and water The organic layer was washed with water, saturated brine dried evaporated The residue was chromatographed over silica gel eluting with a gradient of 10 to 50% ethyl acetate in hexane

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

実験手順: (S)-2-Aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (1.0 g), 4-chloroquinoxaline (0.768 g) and diisopropylethylamine (0.816 ml) were dissolved in tetrahydrofuran (75 ml) and heated to reflux for 6 hours under an atmosphere of argon. After cooling, the reaction solution was partitioned between ethyl acetate and water. The organic layer was washed with saturated sodium hydrogen carbonate solution, saturated brine, dried and evaporated. The residue was chromatographed over silica gel, eluting with a gradient of 50 to 100% ethyl acetate in hexane. The title compound was obtained as a white foam (1.44 g). heated to reflux for 6 hours under an atmosphere of argon After cooling the reaction solution was partitioned between ethyl acetate and water The organic layer was washed with saturated sodium hydrogen carbonate solution, saturated brine dried evaporated The residue was chromatographed over silica gel eluting with a gradient of 50 to 100% ethyl acetate in hexane

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

実験手順: (S)-2-Aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (1.36 g) and 3,4,5-trifluorobenzonitrile (1.00 g) were heated under argon in xylene (10 ml) containing diisopropylethylamine (3.3 ml) for 16 h. The reaction mixture was cooled and partitioned between ethyl acetate and water. The organic phase was washed with brine, dried and evaporated to give a solid which was triturated with pentane-ether to afford the title product (0.16 g) as an off white powder. Chromatography of the mother liquors on silica gel eluting with ethyl acetate-pentane mixtures afforded further title product (0.92 g). Mass Spectrum (API+): Found 252 (MH+-tBoc). C18H23F2N3O2 requires 351. The reaction mixture was cooled partitioned between ethyl acetate and water The organic phase was washed with brine dried evaporated to give a solid which was triturated with pentane-ether