Triethylamine → tert-butyl [2-(7-benzyloxy-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)-1,1-dimethylethyl]carbamate

Participants

Reaction Steps

Ethoxyacetyl chloride (1.82 mL, 16.60 mmol) was added to a chilled (0° C.) solution of tert-butyl [2-(3-amino-7-benzyloxyquinolin-4-ylamino)-1,1-dimethylethyl]carbamate (6.04 g, 13.8 mmol) and triethylamine (3.86 mL, 27.68 mmol) in 150 mL of anhydrous dichloromethane. After stirring for 30 minutes, the cooling bath was removed and the reaction was stirred for 24 hours at ambient temperature. The volatiles were removed under reduced pressure and the resulting residue was dissolved in ethanol, followed by the addition of 3.86 mL of trietylamine. The reaction was heated at reflux for 2.5 days and then cooled to ambient temperature. The solvent was removed under reduced pressure and dichloromethane was added. The solution was sequentially washed with aqueous sodium bicarbonate followed by brine; dried over sodium sulfate; filtered; and concentrated under reduced pressure. The residue was purified using flash column chromatography on silica gel, eluting with 5% methanol in dichloromethane. Clean fractions were concentrated; while fractions containing both the product and the starting material were resubmitted to the reaction conditions and repurified as described above. The combined lots provided a total of 5.07 g of tert-butyl [2-(7-benzyloxy-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)-1,1-dimethylethyl]carbamate was obtained as an orange foam.

Provenance & Evidence