(3-氨基丙基)(2-甲氧基乙基)甲基胺

反应条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of phthalimide 298 (50.0 g, 181 mmol) and N2H4—H2O (17.5 mL, 362 mmol) in EtOH (500 mL) was stirred at reflux temperature for 2 h. The solution was cooled to 5° C. for 2 h, the precipitate filtered, washed with EtOH (5 mL) and the filtrate evaporated to half volume. The solution was cooled at 5° C. for a further 2 h, the precipitate filtered, washed with EtOH (5 mL) and the filtrate evaporated. The residue was dissolved in 1 M HCl (50 mL), washed with Et2O (2×50 mL) and the pH of the aqueous fraction adjusted to 10 with dilute aqueous NH3 solution. The mixture was extracted with CHCl3 (4×50 mL), the combined organic fraction dried and the solvent evaporated to give diamine 299 (Sandberg, R., et al., Acta Pharmaceutica Suecica 1979, 16, 386-395) as a pale yellow oil (25.2 g, 95%) which was used without further purification: 1H NMR [(CD3)2SO] δ 3.38 (t, J=6.0 Hz, 2H, CH2O), 3.21 (s, 3H, OCH3), 2.60 (t, J=6.8 Hz, 2H, CH2N), 2.46 (t, J=6.0 Hz, 2H, CH2N), 2.36 (t, J=7.0 Hz, 2H, CH2N), 2.14 (s, 3H, NCH3), 1.50 (p, J=7.0 Hz, 2H, CH2), NH2 not observed; HRMS (Cl+) calcd for C7H17N2O (M-H+) m/z 145.1341, found 145.1337. at reflux temperature for 2 h the precipitate filtered washed with EtOH (5 mL) the filtrate evaporated to half volume The solution was cooled at 5° C. for a further 2 h the precipitate filtered washed with EtOH (5 mL) the filtrate evaporated The residue was dissolved in 1 M HCl (50 mL) washed with Et2O (2×50 mL) The mixture was extracted with CHCl3 (4×50 mL) the combined organic fraction dried the solvent evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of chloride 21 (2.0 g, 9.03 mmol) and N1-(2-methoxyethyl)-N1-methylpropane-1,3-diamine (297) (2.0 g, 13.6 mmol) in DME (140 mL) was stirred at 20° C. for 18 h, the solvent evaporated and the residue purified by column chromatography, eluting with a gradient (2-15%) of MeOH/DCM, to give 1-oxide 52 (2.3 g, 79%) as a yellow solid: mp 59-61° C.; 1H NMR [(CH3)2SO] δ 7.94 (s, 1H, H-9), 7.68 (br s, 1H, NH), 7.38 (s, 1H, H-5), 3.24-3.44 (m, 6H, CH2), 3.23 (s, 3H, OCH3), 2.92-2.99 (m, 4H, H-6, H-8), 2.56 (br t, J=5.8 Hz, 2H, CH2N), 2.24 (s, 3H, NCH3), 2.03-2.07 (m, 2H, H-7), 1.70-1.74 (m, 2H, CH2); HRMS (FAB+): calcd for C17H26N5O2 (MH+) m/z 332.2087, found, 332.2089. the solvent evaporated the residue purified by column chromatography eluting with a gradient (2-15%) of MeOH/DCM