BrCCCCOC1C=C2C(C=CC(=O)N2)=CC=1.[Na+].[I-].[Cl:20][C:21]1[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:22]=1[N:28]1[CH2:34][CH2:33][CH2:32][N:31]([CH2:35][CH2:36][CH2:37][CH2:38][O:39][C:40]2[CH:49]=[C:48]3[C:43]([CH2:44][CH2:45][C:46](=[O:50])[NH:47]3)=[CH:42][CH:41]=2)[CH2:30][CH2:29]1.C([O-])([O-])=O.[K+].[K+]>CC#N>[Cl:20][C:21]1[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:22]=1[N:28]1[CH2:34][CH2:33][CH2:32][N:31]([CH2:35][CH2:36][CH2:37][CH2:38][O:39][C:40]2[CH:49]=[C:48]3[C:43]([CH:44]=[CH:45][C:46](=[O:50])[NH:47]3)=[CH:42][CH:41]=2)[CH2:30][CH2:29]1A mixture of intermediate 15 (120 mg, 0.41 mmol) and NaI (123 mg, 0.82 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 2 (175 mg, 0.62 mmol) and anhydrous K2CO3 (226 mg, 1.64 mmol) were added to the mixture. The resulting mixture was heated to reflux overnight. The mixture was evaporated under reduced pressure and the residue was extracted with EtOAc. The combined EtOAc layers were washed with brine, dried over anhydrous Na2SO4, concentrated in vacuo and purified by flash chromatography on silica gel column (elution with DCM/MeOH=30:1) to give 7-(4-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-one (compound 4) (50 mg, 26%). 1H NMR (300 MHz, CDCl3) δ 11.54 (br., 1H), 7.71 (d, J=6.9 Hz, 1H) 7.44 (d, J=8.1 Hz, 1H), 7.09-7.07 (m, 2H), 7.01-6.97 (m, 1H), 6.82-6.78 (m, 2H), 6.53 (d, J=9.3 Hz, 1H), 4.10 (t, J=6.6 Hz, 2H), 3.30 (d, J=5.1 Hz, 4H), 2.87-2.81 (m, 4H), 2.62 (t, J=7.5 Hz, 2H), 2.01-1.99 (m, 2H), 1.92-1.82 (m, 2H), 1.76-1.68 (m, 2H). HPLC: 99%, RT 2.461 min. MS (ESI) m/z 460.2 [M+H]+. mp: 55-57° C.
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