N-[2-(4-Nitro-phenyl)-ethyl]-N-[2-(4-phenyl-piperazin-1-yl)-ethyl]-propionamide → 4-(2-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-propyl-amino}-ethyl)-phenylamine

Participants

Reaction Steps

N-[2-(4-nitro-phenyl)-ethyl]-N-[2-(4-phenyl-piperazin-1-yl)-ethyl]-propionamide 28a (0.33 g, 0.80 mmol) was dissolved in dry EtOH (20 mL) and 10 wt % Pd/C (0.05 g) was added. The mixture was stirred for overnight under H2 at 1 atm. Pressure. The reaction mixture was filtered through celite and filtrate was concentrated under reduced pressure and kept under vacuum for 1 h to give the corresponding aniline. In to the solution of the crude product in 15 ml dry THF was added 1 (M) BH3/THF (7 mL, 7 mmol). The reaction mixture was refluxed for 6 h. After the solution was cooled to room temperature, methanol (5 mL) was added slowly. The solvent was removed under reduced pressure and 10% HCl/MeOH (25 mL) was added into the residue and the solution was refluxed for 1 h. Solid NaHCO3 was added and the methanol was removed in vacuo. The mixture was extracted with EtOAc. The combined organic phase was dried over Na2SO4 and evaporated to give the crude product which was purified by chromatography (EtOAc/MeOH=9/1) to give 29a as a colorless oil: 0.23 g (78% yield). 1H NMR (CDCl3, 300 MHz): δ 0.89 (3H, t, J=7.2 Hz, CH3), 1.50 (2H, q, J=7.2 Hz, CH2), 2.48-2.57 (4H, m, CH2Ar, (CH2)N), 2.63-2.75 (10H, m, (CH2)3N, (CH2)2N), 3.20 (4H, t, J=4.8 Hz, (CH2)2NPh), 3.56 (2H, bs, NH2), 6.62 (2H, d, J=8.7 Hz, ArH), 6.85 (1H, t, J=9.6 Hz, ArH), 6.91-6.99 (4H, m, ArH), 7.25 (2H, t, J=9 Hz, ArH). Free base was converted into its hydrochloride salt, mp 262-264° C. Elemental analysis calculated for C23H38N4Cl4, 1.05 H2O: C, 51.99; H, 7.60; N, 10.54. Found C, 52.37; H, 7.89; N, 10.12.

Provenance & Evidence