3-(4-benzylpiperidin-1-yl)propan-1-amine

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: 4-benzyl-1-(3-amino-n-prop-1-yl)piperidine (300 mg, 1.29 mmol, 1 eq) was dissoved in THF at 25° C. under N2 then 3-cyanophenyl isocyanate (186 mg, 1.29 mmol, 1 eq) was added. TLC after 30 minutes shows the reaction complete. The solvent was removed in vacuo then the residue was purified over silica gel in 100% EtOAc to 8:2 chloroform/MeOHto yield 437 mg of an amber oil as product. NMR (300 MHz, DMSO-d6) δ 9.90-9.50 (m, 1H); 9.32 (s, 1H); 7.93 (s, 1H); 7.59 (d, 1H, J=7 Hz); 7.43 (t, 1H, J=7 Hz); 7.40-7.24 (m, 3H); 7.24-7.10 (m, 3H); 6.68 (t, 1H, J=7 Hz); 3.50-3.25 (m, 2H); 3.25-3.07 (m, 2H); 3.07-2.90 (m, 2H); 2.90-2.60 (m, 2H); 2.60-2.40 (m, 2H); 2.00-1.60 (m, 5H); 1.60-1.30 (m, 2H). The solvent was removed in vacuo the residue was purified over silica gel in 100% EtOAc to 8:2 chloroform/MeOHto yield 437 mg of an amber oil as product

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

実験手順: To a stirred solution of 3-(4-benzylpiperidin-1-yl)propionitrile (8.20 g, 35.9 mmol, 1.0 equiv) in anhydrous THF (20 mL) under argon was added a solution of BH3 in THF (1.0 M, 126 mL, 3.5 equiv) at room temperature. The mixture was refluxed for 4.5 hours, then cooled to room temperature and concentrated to a volume of about 30 mL. Aqueous HCl (6 N, 80 mL) was added and stirring was continued for 2 hours at 55-60° C. The mixture was basified to pH 9 by addition of 6 N aq. NaOH and extracted with CH2Cl2 (3×150 mL). The combined organic solutions were dried over MgSO4 and concentrated. The residue was dissolved in CH2Cl2 (20 mL) and treated with HCl in ether (1.0 M, 75 mL, 2.1 equiv). The solvents were removed, ether (60 mL) was added, the mixture was filtered, and the filter cake was washed with ether (2×30 mL). Water (40 mL) was added to the resulting white solid, the pH was adjusted to 10 with 1 M NaOH, and the aqueous phase was extracted with CH2Cl2 (3×80 mL). The combined organic solutions were dried over MgSO4 and concentrated to give 7.59 g (91%) of colorless oil, which was characterized spectroscopically. The mixture was refluxed for 4.5 hours concentrated to a volume of about 30 mL Aqueous HCl (6 N, 80 mL) was added The mixture was basified to pH 9 by addition of 6 N aq. NaOH extracted with CH2Cl2 (3×150 mL) The combined organic solutions were dried over MgSO4 concentrated The residue was dissolved in CH2Cl2 (20 mL) The solvents were removed ether (60 mL) was added the mixture was filtered the filter cake was washed with ether (2×30 mL) Water (40 mL) was added to the resulting white solid the aqueous phase was extracted with CH2Cl2 (3×80 mL) The combined organic solutions were dried over MgSO4 concentrated

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

実験手順: To a solution of 4-benzyl-1-(3-azidopropyl)piperidine (0.14 g, 0.54 mmol) in methanol (5 mL) was added Pd/C 5% (6 mg) and the resulting heterogeneous mixture was hydrogenated at 1 atm for 4 h. then filtered through a celite pad and concentrated in vacuum. The crude compound was purified by trituration with diethyl ether (5 mL) to give the title compound as a white solid (0.075g, 60%), mp 140-141° C. 1H-NMR (DMSO): 1.05-1.21 (m, 2H), 1.35-1.55 (m, 3H), 1.55-1.70 (m, 2H), 1.746 (t, J=11.1 Hz, 2H), 2.281 (t, J=6.6 Hz, 2H), 2.4-2.5 (m, 2H), 2.5-2.85 (m, 4H), 7.06-7.18 (m, 3H), 7.23 (t, J=7.2 Hz, 2H), 7.8 (bs, 2H). then filtered through a celite pad concentrated in vacuum The crude compound was purified by trituration with diethyl ether (5 mL)

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: 4-benzyl-1-(3-amino-n-prop-1-yl)piperidine (300 mg, 1.29 mmol, 1 eq) was dissoved in THF at 25° C. under N2 then 3-cyanophenyl isocyanate (186 mg, 1.29 mmol, 1 eq) was added. TLC after 30 minutes shows the reaction complete. The solvent was removed in vacuo then the residue was purified over silica gel in 100% EtOAc to 8:2 chloroform/MeOH to yield 437 mg of an amber oil as product. NMR (300 MHz, DMSO-d6) δ 9.90-9.50 (m, 1H); 9.32 (s, 1H); 7.93 (s, 1H); 7.59 (d, 1H, J=7 Hz); 7.43 (t, 1H, J=7 Hz); 7.40-7.24 (m, 3H); 7.24-7.10 (m, 3H); 6.68 (t, 1H, J=7 Hz); 3.50-3.25 (m, 2H); 3.25-3.07 (m, 2H); 3.07-2.90 (m, 2H); 2.90-2.60 (m, 2H); 2.60-2.40 (m, 2H); 2.00-1.60 (m, 5H); 1.60-1.30 (m, 2H). The solvent was removed in vacuo the residue was purified over silica gel in 100% EtOAc to 8:2 chloroform/MeOH

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

実験手順: 4-benzyl-1-(3-amino-n-prop-1-yl)piperidine (300 mg, 1.29 mmol, 1 eq) was dissoved in THF at 25° C. under N2 then 3-cyanophenyl isocyanate (186 mg, 1.29 mmol, 1 eq) was added. TLC after 30 minutes shows the reaction complete. The solvent was removed in vacuo then the residue was purified over silica gel in 100% EtOAc to 8:2 chloroform/MeOHto yield 437 mg of an amber oil as product. NMR (300 MHz, DMSO-d6) δ9.90-9.50 (m, 1H); 9.32 (s, 1H); 7.93 (s, 1H); 7.59 (d, 1H, J=7Hz); 7.43 (t, 1H, J=7Hz); 7.40-7.24 (m, 3H); 7.24-7.10 (m, 3H); 6.68 (t, 1H, J=7 Hz); 3.50-3.25 (m, 2H); 3.25-3.07 (m, 2H); 3.07-2.90 (m, 2H); 2.90-2.60 (m, 2H); 2.60-2.40 (m, 2H); 2.00-1.60 (m, 5H); 1.60-1.30 (m, 2H). The solvent was removed in vacuo the residue was purified over silica gel in 100% EtOAc to 8:2 chloroform/MeOHto yield 437 mg of an amber oil as product

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

実験手順: To a stirred solution of 3-(4-benzylpiperidin-1-yl)propionitrile (8.20 g, 35.9 mmol, 1.0 equiv) in anhydrous THF (20 mL) under argon was added a solution of BH3 in THF (1.0M, 126 mL, 3.5 equiv) at room temperature. The mixture was refluxed for 4.5 hours, then cooled to room temperature and concentrated to a volume of about 30 mL. Aqueous HCl (6 N, 80 mL) was added and stirring was continued for 2 hours at 55°-60° C. The mixture was basified to pH 9 by addition of 6N aq. NaOH and extracted with CH2Cl2 (3×150 mL). The combined organic solutions were dried over MgSO4 and concentrated. The residue was dissolved in CH2Cl2 (20 mL) and treated with HCl in ether (1.0M, 75 ml, 2.1 equiv). The solvents were removed, ether (60 mL) was added, the mixture was filtered, and the filter cake was washed with ether (2×30 mL). Water (40 mL) was added to the resulting white solid, the pH was adjusted to 10 with 1M NaOH, and the aqueous phase was extracted with CH2 Cl2 (3×80 mL). The combined organic solutions were dried over MgSO4 and concentrated to give 7.59 g (91%) of colorless oil, which was characterized spectroscopically. The mixture was refluxed for 4.5 hours concentrated to a volume of about 30 mL Aqueous HCl (6 N, 80 mL) was added The mixture was basified to pH 9 by addition of 6N aq. NaOH extracted with CH2Cl2 (3×150 mL) The combined organic solutions were dried over MgSO4 concentrated The residue was dissolved in CH2Cl2 (20 mL) The solvents were removed ether (60 mL) was added the mixture was filtered the filter cake was washed with ether (2×30 mL) Water (40 mL) was added to the resulting white solid the aqueous phase was extracted with CH2 Cl2 (3×80 mL) The combined organic solutions were dried over MgSO4 concentrated

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

実験手順: 4-benzyl-1-(3-amino-n-prop-1-yl)piperidine (300 mg, 1.29 mmol, 1 eq) was dissoved in THF at 25° C. under N2 then 3-cyanophenyl isocyanate (186 mg, 1.29 mmol, 1 eq) was added. TLC after 30 minutes shows the reaction complete. The solvent was removed in vacuo then the residue was purified over silica gel in 100% EtOAc to 8:2 chloroform/MeOHto yield 437 mg of an amber oil as product. NMR (300 MHz, DMSO-d6) δ 9.90-9.50 (m, 1H); 9.32 (s, 1H); 7.93 (s, 1H); 7.59 (d, 1H, J=7 Hz); 7.43 (t, 1H, J=7 Hz); 7.40-7.24 (m, 3H); 7.24-7.10 (m, 3H); 6.68 (t, 1H, J=7 Hz); 3.50-3.25 (m, 2H); 3.25-3.07 (m, 2H); 3.07-2.90 (m, 2H); 2.90-2.60 (m, 2H); 2.60-2.40 (m, 2H); 2.00-1.60 (m, 5H); 1.60-1.30 (m, 2H). The solvent was removed in vacuo the residue was purified over silica gel in 100% EtOAc to 8:2 chloroform/MeOHto yield 437 mg of an amber oil as product

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

実験手順: To a stirred solution of 3-(4-benzylpiperidin-1-yl)propionitrile (8.20 g, 35.9 mmol, 1.0 equiv) in anhydrous THF (20 mL) under argon was added a solution of BH3 in THF (1.0 M, 126 mL, 3.5 equiv) at room temperature. The mixture was refluxed for 4.5 hours, then cooled to room temperature and concentrated to a volume of about 30 mL. Aqueous HCl (6 N, 80 mL) was added and stirring was continued for 2 hours at 55-60° C. The mixture was basified to pH 9 by addition of 6 N aq. NaOH and extracted with CH2Cl2 (3×150 mL). The combined organic solutions were dried over MgSO4 and concentrated. The residue was dissolved in CH2Cl2 (20 mL) and treated with HCl in ether (1.0 M, 75 mL, 2.1 equiv). The solvents were removed, ether (60 mL) was added, the mixture was filtered, and the filter cake was washed with ether (2×30 mL). Water (40 mL) was added to the resulting white solid, the pH was adjusted to 10 with 1 M NaOH, and the aqueous phase was extracted with CH2Cl2 (3×80 mL). The combined organic solutions were dried over MgSO4 and concentrated to give 7.59 g (91%) of colorless oil, which was characterized spectroscopically. The mixture was refluxed for 4.5 hours concentrated to a volume of about 30 mL Aqueous HCl (6 N, 80 mL) was added The mixture was basified to pH 9 by addition of 6 N aq. NaOH extracted with CH2Cl2 (3×150 mL) The combined organic solutions were dried over MgSO4 concentrated The residue was dissolved in CH2Cl2 (20 mL) The solvents were removed ether (60 mL) was added the mixture was filtered the filter cake was washed with ether (2×30 mL) Water (40 mL) was added to the resulting white solid the aqueous phase was extracted with CH2Cl2 (3×80 mL) The combined organic solutions were dried over MgSO4 concentrated

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

実験手順: To a stirred solution of 3-(4-benzylpiperidin-1-yl)propionitrile (8.20 g, 35.9 mmol, 1.0 equiv) in anhydrous THF (20 mL) under argon was added a solution of BH3 in THF (1.0 M, 126 mL, 3.5 equiv) at room temperature. The mixture was refluxed for 4.5 hours, then cooled to room temperature and concentrated to a volume of about 30 mL. Aqueous HCl (6 N, 80 mL) was added and stirring was continued for 2 hours at 55-60° C. The mixture was basified to pH 9 by addition of 6 N aq. NaOH and extracted with CH2Cl2 (3×150 mL). The combined organic solutions were dried over MgSO4 and concentrated. The residue was dissolved in CH2Cl2 (20 mL) and treated with HCl in ether (1.0 M, 75 mL, 2.1 equiv). The solvents were removed, ether (60 mL) was added, the mixture was filtered, and the filter cake was washed with ether (2×30 mL). Water (40 mL) was added to the resulting white solid, the pH was adjusted to 10 with 1 M NaOH, and the aqueous phase was extracted with CH2Cl2 (3×80 mL). The combined organic solutions were dried over MgSO4 and concentrated to give 7.59 g (91%) of colorless oil, which was characterized spectroscopically. The mixture was refluxed for 4.5 hours concentrated to a volume of about 30 mL Aqueous HCl (6 N, 80 mL) was added The mixture was basified to pH 9 by addition of 6 N aq. NaOH extracted with CH2Cl2 (3×150 mL) The combined organic solutions were dried over MgSO4 concentrated The residue was dissolved in CH2Cl2 (20 mL) The solvents were removed ether (60 mL) was added the mixture was filtered the filter cake was washed with ether (2×30 mL) Water (40 mL) was added to the resulting white solid the aqueous phase was extracted with CH2Cl2 (3×80 mL) The combined organic solutions were dried over MgSO4 concentrated

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

実験手順: To a solution of 4-benzyl-1-(3-azidopropyl)piperidine (0.14 g, 0.54 mmol) in methanol (5 mL) was added Pd/C 5% (6 mg) and the resulting heterogeneous mixture was hydrogenated at 1 atm for 4 h. then filtered through a celite pad and concentrated in vacuum. The crude compound was purified by trituration with diethyl ether (5 mL) to give the title compound as a white solid (0.075g, 60%), mp 140-141° C. 1H-NMR (DMSO): 1.05-1.21 (m, 2H), 1.35-1.55 (m, 3H), 1.55-1.70 (m, 2H), 1.746 (t, J=11.1 Hz, 2H), 2.281 (t, J=6.6 Hz, 2H), 2.4-2.5 (m, 2H), 2.5-2.85 (m, 4H), 7.06-7.18 (m, 3H), 7.23 (t, J=7.2 Hz, 2H), 7.8 (bs, 2H). then filtered through a celite pad concentrated in vacuum The crude compound was purified by trituration with diethyl ether (5 mL)