1,1,1-Trimethoxybutane → 3-(7-bromo-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propan-1-ol

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Reaction Steps

A mixture of 3-[(3-amino-7-bromoquinolin-4-yl)amino]propan-1-ol (7.2 g, 24 mmol), pyridine hydrochloride (1.05 g, 9.09 mmol) and trimethyl orthobutyrate (4.05 mL, 25.5 mmol) in toluene (240 mL) was heated at reflux for two hours under an atmosphere of nitrogen. The solvent was removed under reduced pressure, and the residue was dissolved in methanol (100 mL). Aqueous sodium hydroxide (15 mL of 6 M) was added to the solution, and the resulting mixture was stirred for two hours at ambient temperature. A portion of the solvent was removed under reduced pressure, and the resulting mixture was adjusted to pH 7 with the addition of 6 N hydrochloric acid. The mixture was then extracted with chloroform (4×150 mL), and the combined extracts were washed sequentially with saturated aqueous sodium bicarbonate (40 mL) and brine (30 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. An analysis by nuclear magnetic resonance spectroscopy indicated the presence of starting material, and the procedure was repeated using 1 mL trimethyl orthobutyrate and heating at reflux for one hour. Following the work-up procedure, the resulting solid was triturated with ethyl acetate and isolated by filtration to provide 7.30 g of 3-(7-bromo-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propan-1-ol.

Provenance & Evidence