4-pyrrolidin-1-ylbutan-1-amine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a flask under nitrogen, 4-Pyrrolidin-1-yl-butylamine (1.3 equiv, 10.1 g) was taken up in tetrahydrofuran (105 mL, 5 volumes). The mixture was cooled to 0° C. and 1,1′-carbonyldiimidazole (1.3 equiv, 11.6 g) was added. The mixture stirred at 0° C. for 20 minutes, then warmed to 20° C. over 10 minutes and held at 20° C. for 30 minutes. warmed to 20° C. over 10 minutes held at 20° C. for 30 minutes

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-pyrrolidin-1-yl-butylamine (0.180 g, 1.27 mmol) (Seguin, H. et al. Synth. Commun. 1998, 28, 4257-4272), 3,5-dimethyl-pyridine-2-carbaldehyde (0.171 g, 1.27 mmol) and K2CO3 (0.175 g, 1.27) in MeOH (5 mL) was stirred for 20 h. The mixture was filtered through a celite cake and the filtrate was cooled at 0° C. NaBH4 (0.048 g, 1.3 mmol) was added to the filtrate, and the mixture was stirred at for 1 h. Water (20 mL) was added and MeOH was removed. The aqueous residue was extracted with CH2Cl2 (3×20 mL). The organic extracts were combined and dried over anhydrous Na2SO4. After filtration the solvent was removed by evaporation under vacuum, and the residue was purified by flash chromatography on a silica gel column (100:5:3 CH2Cl2/MeOH/NH4OH), affording (3,5-dimethyl-pyridin-2-ylmethyl)-(4-pyrrolidin-1-yl-butyl)-amine as a colorless oil (0.110 g, 33%). 1H NMR (CDCl3) δ 1.54-1.58 (m, 4H), 1.72-1.76 (m, 4H), 2.24 (s, 3H), 2.25 (s, 3H), 2.39-2.46 (m, 6H), 2.66-2.71 (m, 2H), 3.81 (s, 2H), 7.21 (s, 1H), 8.18 (s, 1H). The mixture was filtered through a celite cake the mixture was stirred at for 1 h MeOH was removed The aqueous residue was extracted with CH2Cl2 (3×20 mL) dried over anhydrous Na2SO4 After filtration the solvent was removed by evaporation under vacuum the residue was purified by flash chromatography on a silica gel column (100:5:3 CH2Cl2/MeOH/NH4OH)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-pyrrolidin-1-yl-butylamine (0.180 g, 1.27 mmol) (Seguin, H. et al. Synth. Commun. 1998, 28, 4257-4272), 3,5-dimethyl-pyridine-2-carbaldehyde (0.171 g, 1.27 mmol) and K2CO3 (0.175 g, 1.27) in MeOH (5 mL) was stirred for 20 h. The mixture was filtered through a celite cake and the filtrate was cooled at 0° C. NaBH4 (0.048 g, 1.3 mmol) was added to the filtrate, and the mixture was stirred at for 1 h. Water (20 mL) was added and MeOH was removed. The aqueous residue was extracted with CH2Cl2 (3×20 mL). The organic extracts were combined and dried over anhydrous Na2SO4. After filtration the solvent was removed by evaporation under vacuum, and the residue was purified by flash chromatography on a silica gel column (100:5:3 CH2Cl2/MeOH/NH4OH), affording (3,5-dimethyl-pyridin-2-ylmethyl)-(4-pyrrolidin-1-yl-butyl)-amine as a colorless oil (0.110 g, 33%). 1H NMR (CDCl3) δ 1.54-1.58 (m, 4H), 1.72-1.76 (m, 4H), 2.24 (s, 3H), 2.25 (s, 3H), 2.39-2.46 (m, 6H), 2.66-2.71 (m, 2H), 3.81 (s, 2H), 7.21 (s, 1H), 8.18 (s, 1H). The mixture was filtered through a celite cake the mixture was stirred at for 1 h MeOH was removed The aqueous residue was extracted with CH2Cl2 (3×20 mL) dried over anhydrous Na2SO4 After filtration the solvent was removed by evaporation under vacuum the residue was purified by flash chromatography on a silica gel column (100:5:3 CH2Cl2/MeOH/NH4OH)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from [3-(4-bromo-2,3,6-trifluoro-benzyloxy)-4-carbamoyl-isothiazol-5-yl]-carbamic acid phenyl ester and 4-pyrrolidin-1-yl-butylamine by the procedure analogous to Example 1. MS (APCl, m/z): 550 and 552 [M+H]+.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from [3-(4-bromo-2,3,6-trifluoro-benzyloxy)-4-carbamoyl-isothiazol-5-yl]-carbamic acid phenyl ester and 4-pyrrolidin-1-yl-butylamine by the procedure analogous to Example 1. MS (APCl, m/z): 550 and 552 [M+H]+.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from [4-carbamoyl-3-(2,3,6-trifluoro-4-methyl-benzyloxy)-isothiazol-5-yl]-carbamic acid phenyl ester and 4-pyrrolidin-1-yl-butylamine by the procedure analogous to Example 1. MS (APCl, m/z): 486 [M+H]+.