Methanol → 1-{4-amino-2-(hydroxymethyl)-7-[3-(hydroxymethyl)phenyl]-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-2-(ethoxymethyl)-7-[3-(hydroxymethyl)phenyl]-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol (0.800 g, 1.90 mmol) obtained from the filtrate from the trituration in Example 66, in dichloromethane (20 mL) was cooled to 0° C. Boron tribromide (9.5 mL of a 1 M solution in dichloromethane) was added dropwise, and the resulting suspension was stirred at room temperature for 15 hours. Methanol was carefully added, and the resulting solution was stirred at room temperature for one hour and concentrated under reduced pressure. The residue (1.33 g) was dissolved in DMF (15 mL), and potassium acetate was added. The mixture was heated at 50° C. for 18 hours and then concentrated under reduced pressure. The residue was dissolved in methanol (20 mL) and water (10 mL), and lithium hydroxide monohydrate (1.5 g) was added. The reaction was stirred at room temperature for 64 hours and concentrated under reduced pressure. Methanol and silica gel were added, and the mixture was concentrated under reduced pressure. The residue was purified by automated flash chromatography (FLASH 40+M cartridge, eluting with 7% to 20% 1 M methanolic ammonia in dichloromethane) followed by recrystallization from acetonitrile after a hot filtration. The crystals were washed with acetonitrile and dried in a vacuum oven at 65° C. to provide 146 mg of 1-{4-amino-2-(hydroxymethyl)-7-[3-(hydroxymethyl)phenyl]-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol as a yellow solid, mp 227-229° C.

Provenance & Evidence