N'-(3-methoxypropyl)-N'-methylethane-1,2-diamine

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:; See reaction.notes.procedure_details.

Procedure: A mixture of nitrile 273 (1.94 g, 14.0 mmol), cNH3 (8 mL) and Raney Nickel (50% slurry in water, 5.3 g) in EtOH (100 mL) was stirred under H2 (60 psi) for 4 h. The mixture was filtered through Celite, washed with EtOH (50 mL) and the solvent was evaporated to give crude diamine 274 (1.65 g, 83%) as a yellow oil, which was used without further purification: 1H NMR δ 3.42 (t, J=6.4 Hz, 2H, CH2N), 3.33 (s, 3H, OCH3), 2.76 (t, J=6.1 Hz, 2H, CH2), 2.43 (t, J=7.2 Hz, 2H, CH2), 2.40 (t, J=6.2 Hz, 2H, CH2), 2.21 (s, 3H, NCH3), 1.74 (tt, J=7.2, 6.2 Hz, 2H, CH2), NH2 not observed; MS (APCI) m/z 147 (MH+, 100%); HRMS calcd for C7H18N2O (M+) m/z 146.1419, found 146.1424. The mixture was filtered through Celite washed with EtOH (50 mL) the solvent was evaporated

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

Procedure: A solution of chloride 21 (1.62 g, 7.3 mmol), Et3N (2.0 mL, 14.0 mmol) and N1-(3-methoxypropyl)-N1-methyl-1,2-ethanediamine (274) (1.24 g, 8.8 mmol) in DME (50 mL) was heated at reflux temperature for 18 h. The solution was cooled, the solvent evaporated and the residue partitioned between dilute aqueous NH3 solution (50 mL) and DCM (50 mL). The aqueous layer was extracted with DCM (4×120 mL), the combined organic fraction dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-15%) of MeOH/DCM, to give 1-oxide 32 (1.79 g, 74%) as a yellow solid: mp 41-42° C.; 1H NMR δ 8.07 (s, 1H, H-9), 7.39 (s, 1H, H-5), 5.83 (br s, 1H, NH), 3.55 (dt, J=5.9, 5.5 Hz, 2H, NCH2), 3.43 (t, J=6.3 Hz, 2H, OCH2), 3.33 (s, 3H, OCH3), 3.01 (t, J=7.4 Hz, 2H, H-8), 2.99 (t, J=7.8 Hz, 2H, H-6), 2.64 (t, J=5.9 Hz, 2H, NCH2), 2.50 (t, J=7.2 Hz, 2H, NCH2), 2.27 (s, 3H, NCH3), 2.14 (p, J=7.4 Hz, 2H, H-7), 1.76 (tt, J=7.2, 6.4 Hz, 2H, CH2); 13C NMR δ 158.7, 154.5, 148.8, 143.2, 129.8, 120.5, 114.7, 70.8, 58.6, 55.8, 54.4, 41.6, 38.6, 33.1, 32.3, 27.4, 25.7; MS (APCI) m/z 332 (MH+, 100%). Anal. calcd for C17H25N5O2: C, 61.6; H, 7.6; N, 21.1. Found: C, 61.4; H, 7.4; N, 21.4%. at reflux temperature for 18 h The solution was cooled the solvent evaporated the residue partitioned between dilute aqueous NH3 solution (50 mL) and DCM (50 mL) The aqueous layer was extracted with DCM (4×120 mL) the combined organic fraction dried the solvent evaporated The residue was purified by chromatography eluting with a gradient (0-15%) of MeOH/DCM