Phenol → 4,6-Diamino-2-phenoxy-3-pyridinecarbonitrile

Participants

Reaction Conditions

Reaction Steps

A heavy walled, sealable tube suitable for microwave heating was charged with 60 mg (1.5 mmol) of NaH (60% dispersion in mineral oil) and 3 mL of dioxane. To the suspension was added 150 mg (1.59 mmol) of phenol, then the mixture was stirred for 15 min. Next, 212 mg (1.00 mmol) of 2-bromo-4,6-diaminonicotinonitrile was added. The tube was sealed, and the mixture was heated with a microwave apparatus at 190° C. for 25 minutes then cooled and concentrated under reduced pressure. The residue was diluted with 10 mL of toluene and concentrated again under reduced pressure. The remaining material was taken up in 20 mL of ethyl acetate and extracted with 2M NaOH(aq.) (3×5 mL), and brine (1×5 mL), draining some red precipitate with the aqueous layers. The organic layer was dried over MgSO4, filtered, and concentrated to 178 mg (79%) of an orange solid. The product could be further purified via silica gel chromatography, eluting with 50:50 ethyl acetate:hexanes to provide a white solid. 1H NMR (300 MHz, d6-DMSO) δ 7.38 (m, 2H), 7.17 (m, 1H), 7.10 (m, 2H), 6.37 (s, 2H), 6.25 (s, 2H), 5.41 (s, 1H); MS (ESI) m/e=227 (M+H)+, 225 (M−H)−.

Provenance & Evidence