8-Hydroxyquinoline → HCID 58015559, Verbindung

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To a solution of 1-(2,2-dimethoxyethyl)-5-iodo-1H-indazole (3.14 g, 9.46 mmol) in DMSO (11.2 mL) was added 2-(4-chlorophenyl)-5H-furo[3,2-c]pyridine-4-one (2.32 g, 9.46 mmol), Cs2CO3 (3.39 g, 10.4 mmol), 8-hydroxyquinoline (0.274 g, 1.89 mmol) and CuI (2.16 g, 11.4 mmol). The solution was evacuated for 15 minutes under high vacuum then backfilled with argon. The process was repeated three times. The reaction mixture was stirred at 128° C. for 5 h; then the reaction mixture was cooled to 100° C. and maintained at this temperature for 18 h. The reaction mixture was diluted with 10% NH4OH in H2O (100 mL) and the resulting solids were washed with an additional 10% NH4OH in H2O solution (300 mL). The solids were dissolved in CH2Cl2 (100 mL) and washed with H2O (2×50 mL). The organics were filtered to remove any excess solids and then concentrated. Purification by flash chromatography (silica gel, hexanes with 0.1% Et3N to hexanes/MTBE/EtOAc 35:1.25:0.25 with 0.1% Et3N, to hexanes/MTBE/EtOH 35:1.25:0.25 with 0.1% Et3N, to CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 1:1) yielded the title compound (1.78 g, 41%) as a brown solid: 1H NMR (500 MHz, CDCl3) δ 8.06 (s, 1H), 7.73-7.71 (m, 3H), 7.60 (d, J=9.0 Hz, 1H), 7.43-7.41 (m, 3H), 7.35 (d, J=7.5 Hz, 1H), 7.25 (s, 1H), 6.67 (d, J=7.5 Hz, 1H), 4.78 (t, J=5.5 Hz, 1H), 4.51 (d, J=5.0 Hz, 2H), 3.38 (s, 6H); ESI MS m/z 450 [M+H]+.

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