Methanol → 1-[4-amino-7-(3,4-difluorophenyl)-2-(hydroxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol

Participants

Reaction Conditions

Reaction Steps

A suspension of 1-[4-amino-7-(3,4-difluorophenyl)-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol (0.790 g, 1.85 mmol), obtained from the filtrate from the trituration in Example 59, in dichloromethane (20 mL) was cooled to 0° C. Boron tribromide (5.54 mL of a 1 M solution in dichloromethane) was added dropwise, and the reaction was stirred at room temperature for 22.5 hours. An analysis by LC/MS indicated the reaction was incomplete, and additional boron tribromide (2.7 mL) was added. The reaction was stirred for three hours at room temperature, and then methanol (25 mL) was carefully added. The resulting solution was stirred at room temperature for one hour and concentrated under reduced pressure. A solution of ammonia in methanol (30 mL of 2 M) was added, and the mixture was stirred for 30 minutes and then diluted with methanol (50 mL) and dichloromethane (50 mL). Silica gel was added, and the mixture was concentrated under reduced pressure. The residue was purified by chromatography according to the method described in Example 62. The resulting solid was triturated with acetonitrile, isolated by filtration, washed with acetonitrile, and dried in a vacuum oven to provide 269 mg of 1-[4-amino-7-(3,4-difluorophenyl)-2-(hydroxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol as a light yellow solid, mp 256-258° C.

Provenance & Evidence