2-(1,4-oxazepan-4-yl)ethanamine

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

実験手順: A mixture of nitrile 293 (3.2 g, 22.8 mmol) and Raney-Nickel (50% w/w in water, ca. 12 g) in EtOH (100 mL) and cNH3 (10 mL) was stirred under H2 (60 psi) for 16 h. The mixture was filtered through Celite, washed with EtOH (3×10 mL) and the solvent evaporated to give crude diamine 294 (2.98 g, 91%) as a pale yellow oil, which was used without further purification: 1H NMR [(CD3)2SO] δ 3.64-3.67 (m, 2H, H-3), 3.57-3.59 (m, 2H, H-5), 2.49-2.62 (m, 8H, H-2, H-7, 2×CH2), 1.71-1.80 (m, 2H, H-6), NH2 not observed; HRMS (FAB+) calcd for C7H17N2O (MH+) m/z 145.13409, found 145.13439. The mixture was filtered through Celite washed with EtOH (3×10 mL) the solvent evaporated

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,4-Oxazepane (292) (Turner, S. R. et al., PCT Int. Appl. WO 2000 040561, 2000) (4.95 g, 49.0 mmol) was added dropwise to a stirred aqueous solution of glycolonitrile (55%, 5.3 mL, 53.8 mmol) at 5° C. and stirred at 70° C. for 1 h. More aqueous glycolonitrile (55%, 0.96 mL, 6.13 mmol) was added and the mixture stirred for 30 min, cooled to 20° C. and Et2O (100 mL) and water (50 mL) were added. The aqueous layer was extracted with Et2O (4×30 mL), the combined organic fraction dried and the solvent evaporated to give nitrile 293 (3.24 g, 47%) as a pale yellow oil: 1H NMR δ 3.80-3.84 (m, 2H, H-5), 3.74-3.77 (m, 2H, H-3), 3.60 (s, 2H, CH2CN), 2.79-2.84 (m, 4H, H-2, H-7), 1.92-1.99 (m, 2H, H-6); HRMS calcd for C7H12N2O (M+) m/z 140.0950, found 140.0947. the mixture stirred for 30 min cooled to 20° C. The aqueous layer was extracted with Et2O (4×30 mL) the combined organic fraction dried the solvent evaporated

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

実験手順: A solution of chloride 21 (2.0 g, 9.0 mmol), 2-(1,4-oxazepan-4-yl)ethylamine (292) (1.63 g, 11.3 mmol) and Et3N (1.3 mL, 9.9 mmol) in DME (140 mL) was stirred at reflux temperature for 20 h. The solution was cooled to 20° C., the solvent evaporated and the residue purified by column chromatography, eluting with a gradient (2-6%) of MeOH/DCM, to give (i) starting material 21 (0.5 g, 25%) and (ii) 1-oxide 48 (1.24 g, 42%) as a yellow solid: mp 119-120° C.; 1H NMR δ 8.08 (s, 1H, H-9), 7.40 (s, 1H, H-5), 5.82 (br s, 1H, NH), 3.81 (t, J=6.1 Hz, 2H, CH2O), 3.74 (t, J=4.7 Hz, 2H, CH2), 3.51-3.56 (m, 2H, CH2), 2.97-3.04 (m, 4H, H-6, H-8), 2.73-2.80 (m, 6H, 3×CH2), 2.15 (p, J=7.4 Hz, 2H, H-7), 1.88-1.94 (m, 2H, CH2); 13C NMR δ 158.7, 154.6, 148.8, 143.3, 129.8, 120.5, 114.7, 69.3, 68.7, 57.5, 55.8, 53.6, 38.7, 33.1, 32.3, 30.0, 25.7; HRMS (FAB+) calcd for C17H24N5O2 (MH+) m/z 330.1930, found 330.1937. at reflux temperature for 20 h the solvent evaporated the residue purified by column chromatography eluting with a gradient (2-6%) of MeOH/DCM