O[PH2]=O.[Cl:4][C:5]1[CH:6]=[CH:7][C:8]2[N:9]([C:11]([CH:14]([C:16]3[CH:17]=[C:18]4[C:23](=[CH:24][CH:25]=3)[N:22]=C[CH:20]=[CH:19]4)O)=[CH:12][N:13]=2)[N:10]=1.II>C(O)(=O)C>[Cl:4][C:5]1[CH:6]=[CH:7][C:8]2[N:9]([C:11]([C:14]3[CH:16]=[CH:17][C:18]4[C:23](=[CH:24][CH:25]=[CH:20][CH:19]=4)[N:22]=3)=[CH:12][N:13]=2)[N:10]=1H3PO2 (28.8 mL of a 50% aqueous solution, 263 mmol) was added to a solution of (rac)-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-quinolin-6-yl-methanol (Stage 1.1, 10.89 g, 35.0 mmol) in acetic acid (272 mL) at 80° C. Iodine (13.34 g, 52.6 mmol) was then added and the RM was stirred at 110° C. for 90 min. The RM was cooled down to rt and acetic acid was removed. The residue was taken up in water and DCM. A 2 N NaOH solution was then added until pH=11. The organic layer was then separated and washed with water (2×). The aqueous layer was further extracted with DCM (3×). The combined organic layer was then dried, filtered and concentrated. The residue crystallized in EtOAc. The resulting solid was purified by flash chromatography (Flashmaster, with a 50 g silica gel column, TBME/MeOH: 97:3→84:16). The solid crystallized again in EtOAc/Et2O. It was filtered and dried under vacuum to afford the title compound as a white solid (tR 4.72 min (conditions 4), MH+=295.0, 1H-NMR in DMSO-d6: 8.86 (m, 1H); 8.30 (m, 1H); 8.23 (d, 1H); 7.98 (d, 1H); 7.82 (m, 1H); 7.72 (m, 2H); 7.50 (dd, 1H); 7.35 (d, 1H); 4.52 (s, 2H)).
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