Methanol → n-(1-{[3-(Aminomethyl)phenyl]methyl}-4-hydroxy-1h-indazol-3-yl)-5-chloro-2-thiophenesulfonamide formate salt

関与物質

反応手順

A suspension of N-[1-{[3-(aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide hydrochloride (for a preparation see Intermediate 4) (266 mg, 0.533 mmol) in anhydrous DCM (7.5 mL) under nitrogen atmosphere was treated dropwise with boron tribromide solution in DCM (1M, 0.533 mL, 0.533 mmol) at room temperature, and the reaction mixture was stirred at room temperature for 1 hour (reaction not in solution—sticky orange gum had formed). A further portion of boron tribromide (1M, 0.533 mL) was added and the reaction mixture was stirred at room temperature for 1 hour (reaction still not in solution). Anhydrous methanol was added dropwise until the reaction was in solution. Reaction mixture was then stirred at room temperature for a further 30 min. Saturated aqueous sodium bicarbonate solution (10 mL) was added dropwise with care to quench the reaction, on addition of which both a white precipitate (suspended in the aqueous layer) and a dark green sticky gum (stuck to the side of the flask) formed. The aqueous and organic layers were applied to a hydrophobic frit and the organic layer collected and retained. The remaining green gum in the flask was dissolved in 1:1 methanol-dichloromethane, passed through a hydrophobic frit, combined with the retained organic and evaporated in-vacuo to yield a dark green sticky solid (265 mg). This was dissolved in DMSO (3×1 mL) and purified by MDAP Sunfire C18 column, eluting with solvents A/B (A: 0.1% v/v solution of formic acid in water, B: 0.1% v/v solution of formic acid in acetonitrile) (25 min run). Appropriate fractions were combined and evaporated in-vacuo to yield the title compound as a colourless oil (86 mg, 33%). LCMS (System B) RT=1.63 min, ES+ve m/z 449/451 (M+H)+.

情報源と証拠