2-methoxy-7-(pyrimidin-5-yl)-9H-xanthen-9-one → 2-methoxy-7-(pyrimidin-5-yl)-9-vinyl-9H-xanthen-9-ol

Participants

Reaction Conditions

Reaction Steps

A vial charged with Pd2(dba)3 (0.150 g, 0.164 mmol), XPhos (0.391 g, 0.819 mmol), 5-(tributylstannyl)pyrimidine (1.81 g, 4.92 mmol), 2-bromo-7-methoxy-9H-xanthen-9-one (1.000 g, 3.28 mmol) and dioxane (10 mL). The reaction mixture was evacuated and backfilled with nitrogen. The reaction mixture was heated to 100° C. overnight. The reaction mixture was cooled to RT and diluted with water and EtOAc. A grey solid precipitated out, which was filtered off. The solid was washed with EtOAc and water. The grey solid dried under reduced pressure to afford 2-methoxy-7-(pyrimidin-5-yl)-9H-xanthen-9-one) (0.600 g, 60.2% yield). Step 2: A solution of vinylmagnesium chloride (1.6M solution in THF; 0.82 mL, 1.314 mmol) was added dropwise to a solution of 2-methoxy-7-(pyrimidin-5-yl)-9H-xanthen-9-one (200 mg, 0.657 mmol) in THF (10 mL) at −78° C. After 30 min, the reaction mixture was allowed to warm to −10° C. and was then quenched with saturated aqueous ammonium chloride. The reaction was extracted with EtOAc, and the organic phase was dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by chromatography to give 2-methoxy-7-(pyrimidin-5-yl)-9-vinyl-9H-xanthen-9-ol as a pale yellow gum. Step 3: 2 N HCl (3 mL) was added to solution of 2-methoxy-7-(pyrimidin-5-yl)-9-vinyl-9H-xanthen-9-ol (50 mg, 0.150 mmol) and thiourea (9.25 μL, 0.171 mmol) in HOAc (5 mL). The reaction mixture was allowed to stir overnight at rt and concentrated under reduced pressure. The residue was treated with of TFA (4 mL). The reaction mixture was stirred overnight at rt. The reaction mixture was concentrated under reduced pressure and the residue was treated with aqueous, half-saturated sodium bicarbonate, extracted with EtOAc, and concentrated under reduced pressure. The residue was purified by chromatography (DCM/MeOH 20:1 to 5:1) to give 2′-methoxy-7′-(pyrimidin-5-yl)-5,6-dihydrospiro[[1,3]thiazine-4,9′-xanthen]-2-amine as an off-white solid.

Provenance & Evidence