[O:1]=[C:2]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:5][CH:4]([C:15]([O:17][CH3:18])=[O:16])[NH:3]1.[H-].[Na+].C1(P(C2C=CC=CC=2)(O[NH2:30])=O)C=CC=CC=1>CN(C=O)C>[NH2:30][N:3]1[C:2](=[O:1])[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:5][CH:4]1[C:15]([O:17][CH3:18])=[O:16]1-(tert-Butyl) 3-methyl 5-oxo-1,3-piperazinedicarboxylate (3.15 g) was dissolved in DMF (63 ml) and combined with sodium hydride (0.59 g, in oil) with cooling on ice. The mixture was stirred at 50° C. for 1 hour and then cooled to room temperature, combined with O-diphenylphosphinyl hydroxylamine (3.13 g), and stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and the residue was combined with aqueous sodium bicarbonate and extracted with dichloromethane. The extract was dried and concentrated to obtain 1-(tert-butyl) 3-methyl 4-amino-5-oxo-1,3-piperazine dicarboxylate as a yellow oil. A mixture of this material and 1-(2-methyl-4-pyridinyl)-4-piperidone (2.3 g) in ethanol (63 ml) was dehydrated using a Soxlet extractor packed with molecular sieves 4A while refluxing for 15 hours. The reaction mixture was concentrated, and the residue was dissolved in methanol (63 ml), combined with acetic acid (1.45 ml) with cooling on ice, followed by sodium cyanoborohydride (1.53 g), and then stirred at room temperature for 2 hours. The reaction mixture was concentrated, and the residue was dissolved in ethyl acetate, washed with aqueous sodium bicarbonate and brine, dried, concentrated and purified by a column chromatography on a basic silica gel (ethyl acetate:methanol=20:1) to obtain the title compound (3.4 g) as a pale yellow non-crystalline powder.
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