Hydrochloric Acid → 1-[4-amino-2-(2-hydroxyethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol

Participants

Reaction Steps

A solution of boron tribromide in dichloromethane (22.71 mL of 1 M) was added to a chilled (0° C.) suspension of 1-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol hydrobromide (3.00 g, 7.57 mmol) in dichloromethane (100 mL). The reaction mixture was allowed to come to ambient temperature with stirring for 16 hours. Methanol (30 mL) and hydrochloric acid (30 mL of 6 N) were added and the reaction mixture was heated at reflux for 2.5 hours. The reaction mixture was made basic with sodium hydroxide and the layers were separated. The aqueous layer was extracted with dichloromethane (100 mL). The extract was washed sequentially with water and brine, dried over magnesium sulfate, and then concentrated under reduced pressure to provide a pink solid. This material was crystallized from acetonitrile to provide 0.68 g of 1-[4-amino-2-(2-hydroxyethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol. The aqueous layer was combined with the water and brine washings and allowed to stand overnight. A precipitate was isolated by filtration, washed with water, and dried under vacuum at 95° C. for 3 hours to provide 1.16 g of 1-[4-amino-2-(2-hydroxyethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol as a pink crystalline solid, mp 194-195° C. Anal. calcd for C15H19N5O2: % C, 59.79; % H, 6.36; % N, 23.24. Found: % C, 59.51; % H, 6.59; % N, 23.34.

Provenance & Evidence