N-bromobutanimide → HCID 24957431, compound

Participants

Reaction Steps

6-Methoxyisoquinoline-1-ol was prepared as described above, followed by deprotection of the methoxy group using chlorobenzene and boron tribromide (6 equivalents, neat) added dropwise under argon atmosphere at room temperature, to obtain isoquinoline-1,6-diol (14v). Compound 14v (11.5 mmol) reacted with 4-iodoanisole (4.01 g, 17.13 mmol), copper (I) iodide (0.44 g, 2.28 mmol). L-proline (0.53 g, 4.57 mmol) and anhydrous potassium carbonate (3.16 g, 22.84 mmol) were placed in a dry 250 mL three-necked round-bottomed flask fitted with a stirring bar and reflux condenser. The reaction flask was vacuumed and refilled with dry argon. 50 mL of anhydrous methyl sulfoxide was added via syringe. The reaction mixture was stirred and heated to 130° C. for 20 hours. 50 mL of water was added to quench the reaction, and solid precipitated out. The solid was filtered, washed with water (2×20 mL) and dried in air. This solid was purified by flash column chromatography (silica gel, ethyl acetate) to give 6-hydroxy-2-(4-methoxyphenyl)isoquinolin-1(2H)-one (14w) a brown solid product. Compound 14w (1.8 mmol) was placed in a dry 250 mL single-necked round-bottomed flask fitted with a stirring bar and septa. Acetonitrile (10 mL) was added via a syringe under argon atmosphere at room temperature. N-Bromosuccinimide or NBS (0.33 g, 1.87 mmol) was added portionwise under argon atmosphere at room temperature. The reaction mixture was allowed to stir at room temperature for 2 hours. 20 mL of saturated sodium bicarbonate solution was then added. The mixture was extracted with ethyl acetate (3×10 mL). Organic layers were separated, dried over anhydrous magnesium sulfate and concentrated under vacuum. The residue was purified by flash column chromatography (silica gel, hexanes/EtOAc=2/3 v/v) to give white solid of 4-bromo-6-hydroxy-2-(4-methoxyphenyl)isoquinolin-1(2H)-one (14xME)

Provenance & Evidence