[CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][N:7]1[C:17](=[O:18])[CH2:16][NH:15][C:14](=O)[CH:13]=[C:8]12.O=P(Cl)(Cl)Cl.[CH:25]([C:28]1[N:29]=[CH:30][NH:31][CH:32]=1)([CH3:27])[CH3:26].C([O-])(O)=O.[Na+]>ClCCCl>[CH:25]([C:28]1[N:29]=[CH:30][N:31]([C:14]2[CH:13]=[C:8]3[C:9]4[C:4]([CH2:5][CH2:6][N:7]3[C:17](=[O:18])[CH2:16][N:15]=2)=[C:3]([O:2][CH3:1])[CH:12]=[CH:11][CH:10]=4)[CH:32]=1)([CH3:27])[CH3:26]To a stirred solution of 9-methoxy-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione (80 mg, 0.31 mmol) in 1,2-dichloroethane (8 mL) was added POCl3 (0.058 mL, 0.62 mmol) and the resulting yellow suspension was stirred at 100° C. for 1 h. The reaction mixture was cooled to RT and concentrated under reduced pressure to dryness. The resulting crude chloro compound was dissolved in 1,2-dichloroethane (8 mL), 4-isopropyl-1H-imidazole (102 mg, 0.93 mmol) was added and the mixture was stirred at 100° C. for 2 h. The reaction mixture was allowed to warm to RT. Saturated aqueous NaHCO3 solution was added and the mixture was extracted twice with DCM. The combined organic layers were dried with sodium sulfate, filtered and the solvent was removed under reduced pressure. The crude product was purified by flash-column chromatography over silicagel (eluent: gradient 0% to 100% ethyl acetate/cyclohexane in 30 min) to yield 15 mg of a brown solid. Further purification by SFC (column: Diol 5 μm, 250×30 mm, 60A, Princeton; eluent: 13% MeOH/CO2 for 0.5 min, then from 13% MeOH/CO2 to 18% MeOH/CO2 in 6 min; then from 18% MeOH/CO2 to 50% MeOH/CO2 in 1 min; flow 100 mL/min; UV detection at 220 nm) yielded the title compound (9 mg). UPLC-MS: MS 351.3 (M+H+); UPLC rt 0.90 min. 1H NMR (400 MHz, CHLOROFORM-d): δ ppm 1.35 (d, J=6.8 Hz, 6 H), 2.95 (t, J=6.2 Hz, 2 H), 3.03-3.19 (m, 1 H), 3.88 (s, 3 H), 3.92-4.05 (m, 2 H), 4.40 (s, 2 H), 6.87-7.05 (m, 2 H), 7.19-7.58 (m, 4 H).
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