4-Toluenesulfonyl chloride → HCID 86612244, compound

Participants

Reaction Steps

3-Chloroperoxybenzoic acid (3.43 g of 70%, 19.9 mmol, 2.0 eq) was added to a solution of 4-(2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyraldehyde O-methyloxime (3.1 g, 9.96 mmol, 1.0 eq) in chloroform (45 mL). The reaction was stirred at ambient temperature for one hour. Analysis by thin layer chromatography indicated that the reaction was incomplete so additional 3-chloroperoxybenzoic acid (0.70 g) was added. After one additional hour of string, ammonium hydroxide (12 mL of 15M) and p-toluenesulfonyl chloride (2.1 g, 11 mmol, 1.1 eq) were added dropwise. The reaction mixture was stirred for an additional hour, filtered to remove the resulting white solid, and diluted with dichloromethane (60 mL) and saturated aqueous sodium bicarbonate (75 mL). The phases were separated and the aqueous phase was extracted with dichloromethane (2×20 mL). The combined organics were dried over magnesium sulfate, filtered, and then concentrated under reduced pressure to provide a dark orange oil. The material was triturated with acetonitrile to afford 0.94 g of 4-(4-amino-2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyraldehyde O-methyloxime as a tan solid material. The filtrate from the trituration was purified by BIOTAGE HORIZON High-Performance Flash Chromatography (HPFC) instrument (eluting with chloroform/methanol/ammonium hydroxide (CMA) (80/18/2):chloroform ranging in ratios from 0:100 to 25:75) to provide an additional 0.84 g of product.

Provenance & Evidence