Reaktion #156351

Reaktionsgleichung

Iodine

H3PO2

(rac)-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-quinolin-6-yl-methanol

→

title compound

(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-quinoline

Lösungsmittel

acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe RM was cooled down to rt
2. 2
   Sonstigeacetic acid was removed
3. 3
   workup.ADDITIONA 2 N NaOH solution was then added until pH=11
4. 4
   SonstigeThe organic layer was then separated
5. 5
   Waschenwashed with water (2×)
6. 6
   ExtraktionThe aqueous layer was further extracted with DCM (3×)
7. 7
   SonstigeThe combined organic layer was then dried
8. 8
   Filtrationfiltered
9. 9
   Einengenconcentrated
10. 10
    SonstigeThe residue crystallized in EtOAc
11. 11
    SonstigeThe resulting solid was purified by flash chromatography (Flashmaster
12. 12
    SonstigeThe solid crystallized again in EtOAc/Et2O
13. 13
    FiltrationIt was filtered
14. 14
    Sonstigedried under vacuum

Vorschrift

H3PO2 (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)).

Quelle