3-Aminoquinoline → 6-(furan-2-ylsulfonyl)-N-quinolin-3-yl-7,8-dihydro-5H-2,6-naphthyridin-1-amine

Participants

Reaction Conditions

Reaction Steps

The yellow residue containing 5-chloro-2-(furan-2-ylsulfonyl)-1,2,3,4-tetrahydro-2,6-naphthyridine (0.057 g, 0.19 mmol) and quinolin-3-amine (0.096 g, 0.67 mmol) from 02910-38 was dissolved in toluene (1 mL) and tert-butanol (0.170 mL). The resulting yellow solution was degassed (vacuum) and then tris(dibenzylideneacetone)dipalladium(0) (4.19 mg, 4.58 µmol), Xantphos (5.52 mg, 9.54 µmol), and sodium tert-butoxide (0.026 g, 0.27 mmol) were added. Another 2 mL of toluene and 0.340 mL of tert-butanol were also added. The resulting mixture was subjected to microwave conditions for 30 min (300W, 110°C) and then cooled. The biphasic red-brown/brown-black mixture was poured into saturated aqueous sodium chloride and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated. The resulting residue was purified by falsh column chromatography (SiO2, 0-100% ethyl acetate in hexanes) and then preparative LCMS (C18, ethanol in water containing ammonium carbonate, pH 10). The resulting white solid was repurified a third time via preparative HPLC (C18, acetonitrile in water containing ammonium carbonate, pH 10) to afford 6-(furan-2-ylsulfonyl)-N-(quinolin-3-yl)-5,6,7,8-tetrahydro-2,6-naphthyridin-1-amine (7.60 mg, 9.80 %) of 95% purity as a white solid.

Provenance & Evidence