Acetic Acid → 5-Chloro-7-(6-methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol

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Reaction Conditions

Reaction Steps

5-Chloro-7-(6-methoxy-pyridin-3-yl)-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (114 mg, 0.372 mmol) was dissolved in Methanol (12.0 mL): Tetrahydrofuran (8.0 mL), Acetic acid (0.200 mL, 3.52 mmol) was added followed by Sodium Tungstate Dihydrate (7.0 mg, 0.021 mmol) and 50% Hydrogen Peroxide (0.100 mL, 1.76 mmol) and the mixture was heated at 60-80° C. overnight in a vial. LCMS shows conversion to a mixture of sulfoxide and sulfone. The mixture was cooled, added portionwise to stirring water (60 mL) and let stand. The solids were collected, washing with water. The crude 5-Chloro-2-methanesulfonyl-7-(6-methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazine was suspended in 1,4-Dioxane (3.00 mL): 5.0 M of Sodium hydroxide in Water (0.50 mL, 2.5 mmol) and heated at 60° C. for 2 h, then cooled and treated with Acetic acid (0.200 mL, 3.52 mmol) and water (1 mL). The solids were let stand 1 h, then collected. Product was also in the aq. layer, which was extr. with DCM (3×20 mL), comb. with the solids and conc. in vacuo onto 3 g silica gel. Purification (ISCO, 0-80% EtOAc:Hex) afforded 5-Chloro-7-(6-methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-ol (31 mg; Yield=30%) as yellow solids.

Provenance & Evidence