Propylamine → 1-[4-amino-7-(1,3-dioxolan-2-ylmethoxy)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol

Participants

Reaction Conditions

Reaction Steps

[7-Benzyloxy-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol was prepared according to a modification of the methods described in Parts A-H of Example 2, with 3-benzyloxyaniline, 1-amino-2-methylpropan-2-ol, and 3-methoxypropanoyl chloride used in lieu of 4-benzyloxyaniline, propylamine, and ethoxyacetyl chloride, respectively. The general methods described in Parts H through J of Example 1 were used to convert [7-benzyloxy-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol to 4-amino-1-(2-hydroxy-2-methylpropyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-7-ol. A mixture of 4-amino-1-(2-hydroxy-2-methylpropyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-7-ol (375 mg, 1.13 mmol), 2-bromomethyl-1,3-dioxolane (208 mg, 1.24 mmol) and potassium carbonate (312 mg, 2.26 mmol) in DMF (15 mL) was heated at 70° C. overnight. The temperature was increased to 130° C. and additional 2-bromomethyl-1,3-dioxolane and potassium carbonate were added over 3 days. The reaction mixture was allowed to cool to room temperature, then was filtered to remove the solids. The filtrate was concentrated under reduced pressure and the residue was slurried in dichloromethane. Again, the solids were removed by filtration and the filtrate was concentrated under reduced pressure. Purification by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-35% methanol/dichloromethane (20:80) in dichloromethane) followed by recrystallization from acetonitrile provide 20 mg of 1-[4-amino-7-(1,3-dioxolan-2-ylmethoxy)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol as off white crystals, mp 131.0-136.0° C.

Provenance & Evidence