Ammonia → 3-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)-2,2-dimethylpropanamide

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Reaction Steps

A modification of the methods described in Part C of Example 61 was used to treat methyl 3-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)-2,2-dimethylpropanoate (1.61 g, 5.4 mmol) with potassium hydroxide (22 mL of 0.5 M); the reaction was heated at reflux overnight. The reaction with oxalyl chloride (0.96 mL) in dichloromethane (55 mL total) was stirred for one hour before more oxalyl chloride (1.0 mL) and DMF (three drops) were added, and then the reaction was stirred overnight. The precipitate isolated after the reaction with ammonia and treatment with sodium bicarbonate was combined with material from another run and recrystallized from methanol/water. The resulting solid was isolated by filtration and heated gently in a mixture of methanol (35 mL), water (10 mL), and concentrated hydrochloric acid (0.83 mL). The mixture was filtered to remove a small amount of insoluble material, and a precipitate formed in the filtrate. The precipitate was isolated by filtration, recrystallized twice from methanol/water, dried overnight in a vacuum oven at 70° C., and recrystallized four times from ethyl acetate/methanol/water with a filtration through a 20 micron filter prior to the last two crystallizations. The resulting crystals were dried overnight in a vacuum oven at 70° C. to provide 3-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)-2,2-dimethylpropanamide as white crystals, mp 287-289° C.

Provenance & Evidence