2-(4-benzylpiperidin-1-yl)ethanamine

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of N-(2-aminoethyl)-4-benzylpiperidine (13.0 g, 59.6 mmol), 1,8-diazabicyclo[5,4,0]-7-undecene (10.9 g, 71.7 mmol) and N,N-dimethylformamide (90.0 ml, 1.16 mol) was chilled to -30° C. To the mixture was added over 30 minutes a solution of (2S, 4S)-6-fluoro-2',5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carbonyl chloride (Reference Example, 18.0 g, 60.3 mmol) in N,N-dimethylformamide (90.0 ml, 1.16 mol) and the mixture was stirred for 15 hours at temperature of 15°-25° C. After distilling off the solvent, the reaction mixture was chromatographed on silica gel, eluted with CH2Cl2 /MeOH (9/1) and evaporated in vacuo to dryness to give the desired compound (14.3 g, 50.0%) as colorless amorphous substance. After distilling off the solvent the reaction mixture was chromatographed on silica gel eluted with CH2Cl2 /MeOH (9/1) evaporated in vacuo to dryness

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of N-(2-aminoethyl)-4-benzylpiperidine (13.0 g, 59.6 mmol), 1,8-diazabicyclo[5,4,0]-7-undecene (10.9 g, 71.7 mmol) and N,N-dimethylformamide (90.0 ml, 1.16 mol) was chilled to -30° C. To the mixture was added over 30 minutes a solution of (2S, 4S)-6-fluoro-2',5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carbonyl chloride (Reference Example, 18.0 g, 60.3 mmol) in N,N-dimethylformamide (90.0 ml, 1.16 mol) and the mixture was stirred for 15 hours at temperature of 15°-25° C. After distilling off the solvent, the reaction mixture was chromatographed on silica gel, eluted with CH2Cl2 /MeOH (9/1) and evaporated in vacuo to dryness to give the desired compound (14.3 g, 50.0%) as colorless amorphous substance. After distilling off the solvent the reaction mixture was chromatographed on silica gel eluted with CH2Cl2 /MeOH (9/1) evaporated in vacuo to dryness

反応条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of N-(2-aminoethyl)-4-benzylpiperidine (13.0 g, 59.6 mmol), 1,8-diazabicyclo[5,4,0]-7-undecene (10.9 g, 71.7 mmol) and N,N-dimethylformamide (90.0 ml, 1.16 mol) was chilled to -30° C. To the mixture was added over 30 minutes a solution of (2S, 4S)-6-fluoro-2',5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carbonyl chloride (Reference Example, 18.0 g, 60.3 mmol) in N,N-dimethylformamide (90.0 ml, 1.16 mol) and the mixture was stirred for 15 hours at temperature of 15°-25° C. After distilling off the solvent, the reaction mixture was chromatographed on silica gel, eluted with CH2Cl2 /MeOH (9/1) and evaporated in vacuo to dryness to give the desired compound (14.3 g, 50.0%) as colorless amorphous substance. After distilling off the solvent the reaction mixture was chromatographed on silica gel eluted with CH2Cl2 /MeOH (9/1) evaporated in vacuo to dryness

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

実験手順: A suspension of 2-(4-benzylpiperidino)-1-ethanamine (Example B1, 54.6 mg, 0.25 mmol), TEA (35 μL, 0.25 mmol) and 1,3-bis-(2,6-dimethyl-pyridin-4-yl)-urea (Example B1, 67.6 mg 0.25 mmol) in dioxane (2 mL) is heated at reflux for 24 h. The solvent is evaporated and the residue purified by HPLC to provide the title compound. is heated at reflux for 24 h The solvent is evaporated the residue purified by HPLC

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of CDI (178 mg, 1.1 mmol) in DMSO (5 mL) is added a solution of 2-(4-benzyl-piperidin-1-yl)-ethylamine (218 mg, 1 mmol) in DMSO (1 mL). The reaction mixture is stirred at 20° C. for 3 h. Methyl-(2-methyl-quinolin-4-yl)-amine (173 mg, 1 mmol) is added. To the resulting solution is added in a single portion NaHMDS (2 M in THF, 1.25 mL, 2.5 mmol). The reaction mixture is stirred at 20° C. for 24 h, then H2O (0.4 mL) is added. The reaction mixture is evaporated and the residue purified by preparative HPLC to provide the title compound. The reaction mixture is stirred at 20° C. for 24 h The reaction mixture is evaporated the residue purified by preparative HPLC

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of CDI (178 mg, 1.1 mmol) in DMSO (5 mL) is added a solution of 2-(4-benzyl-piperidin-1-yl)-ethylamine (218 mg, 1 mmol) in DMSO (1 mL). The reaction mixture is stirred at 20° C. for 3 h. Methyl-(2-methyl-quinolin-4-yl)-amine (173 mg, 1 mmol) is added. To the resulting solution is added in a single portion NaHMDS (2 M in THF, 1.25 mL, 2.5 mmol). The reaction mixture is stirred at 20° C. for 24 h, then H2O (0.4 mL) is added. The reaction mixture is evaporated and the residue purified by preparative HPLC to provide the title compound. The reaction mixture is stirred at 20° C. for 24 h The reaction mixture is evaporated the residue purified by preparative HPLC

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of CDI (178 mg, 1.1 mmol) in DMSO (5 mL) is added a solution of 2-(4-benzyl-piperidin-1-yl)-ethylamine (218 mg, 1 mmol) in DMSO (1 mL). The reaction mixture is stirred at 20° C. for 3 h. Methyl-(2-methyl-quinolin-4-yl)-amine (173 mg, 1 mmol) is added. To the resulting solution is added in a single portion NaHMDS (2 M in THF, 1.25 mL, 2.5 mmol). The reaction mixture is stirred at 20° C. for 24 h, then H2O (0.4 mL) is added. The reaction mixture is evaporated and the residue purified by preparative HPLC to provide the title compound. The reaction mixture is stirred at 20° C. for 24 h The reaction mixture is evaporated the residue purified by preparative HPLC

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

実験手順: [2-(4-Benzyl-piperidin-1-yl)-ethyl]-carbamic acid tert-butyl ester (1.34 g, 4.2 mmol) is dissolved in CHCl3 (3 mL) and treated with TFA (3 mL) for 2 h at 20° C. The solvent is evaporated, the residue dissolved CH2Cl2 (100 mL) and washed with 1M aqueous NaOH (2×30 mL). The organic layer is dried (Na2SO4), filtered and concentrated to provide the title compound. The solvent is evaporated the residue dissolved CH2Cl2 (100 mL) washed with 1M aqueous NaOH (2×30 mL) The organic layer is dried (Na2SO4) filtered concentrated

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

実験手順: [2-(4-Benzyl-piperidin-1-yl)-ethyl]-carbamic acid tert-butyl ester (1.34 g, 4.2 mmol) is dissolved in CHCl3 (3 mL) and treated with TFA (3 mL) for 2 h at 20° C. The solvent is evaporated, the residue dissolved CH2Cl2 (100 mL) and washed with 1M aqueous NaOH (2×30 mL). The organic layer is dried (Na2SO4), filtered and concentrated to provide the title compound. The solvent is evaporated the residue dissolved CH2Cl2 (100 mL) washed with 1M aqueous NaOH (2×30 mL) The organic layer is dried (Na2SO4) filtered concentrated