[CH2:1]([O:3][C:4](=[O:20])[CH2:5][C:6]1[C:11](N)=[CH:10][N:9]=[C:8]([N:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[CH:7]=1)[CH3:2].N([O-])=O.[Na+].[Na+].[Cl-:26]>Cl.O.CCOC(C)=O.[Cu]Cl>[CH2:1]([O:3][C:4](=[O:20])[CH2:5][C:6]1[C:11]([Cl:26])=[CH:10][N:9]=[C:8]([N:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[CH:7]=1)[CH3:2][5-Amino-2-(4-methyl-piperazin-1-yl)-pyridin-4-yl]-acetic acid ethyl ester (680 mg, 2.44 mmol) is dissolved under an atmosphere of argon in 18% aqueous hydrochloric acid (12 ml). After cooling the solution to 0° C., a solution of sodium nitrite (244 mg, 3.54 mmol) in water (6 ml) is added over 15 minutes, taking care that the internal temperature did not rise above 5° C. After 20 minutes at 0° C., the reaction mixture is added to a −10° C. solution of copper(I) chloride (freshly prepared, 725 mg, 7.33 mmol) in water (1.8 ml). After 15 minutes at −10° C., TLC analysis indicated complete conversion. The reaction mixture is diluted with EtOAc and poured in a saturated aqueous NaCl solution. The organic layer is separated, dried over Na2SO4, and concentrated. The residue is purified by FCC (CH2Cl2/MeOH, gradient from 98:2 to 90:10) to afford the title compound. 1H NMR (CDCl3, 400 MHz): δ 1.27 (t, J=7 Hz, 3H), 2.34 (s, 3H), 2.50 (m, 4H), 3.52 (m, 4H), 3.66 (s, 2H), 4.19 (q, J=7 Hz, 2H), 6.59 (s, 1H), 8.11 (s, 1H). ES+−MS: 298.2, 300.1 (Cl) [M+H]+, ES−−MS: 296.2, 298.2 (Cl) [M−H]−.
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