Toluene → (S)-N-(7-((3-ethoxypyridin-2-yl)amino)-4-fluoro-9-(2-hydroxyethyl)-2-methoxy-9H-xanthen-9-yl)cyanamide

Participants

Reaction Steps

A 20 mL resealable tube was charged with 3-ethoxypyridin-2-amine (176 mg, 1.272 mmol), (S)-7′-bromo-4′-fluoro-2′-methoxy-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-2-amine (250 mg, 0.636 mmol), Pd2 dba3 (29.1 mg, 0.032 mmol), t-BuXPhos (47.2 mg, 0.111 mmol) and sodium t-butoxide (244 mg, 2.54 mmol). Toluene (6 ml) was added, the mixture was stirred for 2 min at room temperature, then heated at 100° C. for 1.5 hr. The solution was diluted with ethyl acetate and water. The organic layer was separated and concentrated. The product was purified via silica gel column chromatography (RediSep 40 g column) using 20-80% ethyl acetate in heptane to afford (S)—N-(7-((3-ethoxypyridin-2-yl)amino)-4-fluoro-9-(2-hydroxyethyl)-2-methoxy-9H-xanthen-9-yl)cyanamide (160 mg, 0.355 mmol, 55.9% yield). MS m/z=451.0 [M+H].

Provenance & Evidence