Acetic Anhydride → HCID 57657239, compound

Participants

Reaction Steps

A solution of 1-[4-amino-7-(3-aminopropyl)-2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol (1.25 g, 3.50 mmol) in triethylamine (2.4 mL, 17.5 mmol) was cooled to 0° C. in an ice water bath and acetic anhydride (393 mg, 3.85 mmol) was added. The solution was stirred for approximately 18 hours while warming to ambient temperature. The solution was concentrated under reduced pressure and the residue was partitioned between 1% aqueous sodium carbonate (125 mL) and chloroform (50 mL). Successive chloroform extractions were performed until no product was present in the aqueous layer. The combined organic fractions were concentrated under reduced pressure and dissolved in methanol (100 mL). To this solution was added solid potassium carbonate (3 tsp) and the reaction was heated to reflux temperature for 2 hours. After cooling to ambient temperature, the mixture was filtered, concentrated and partitioned between water (50 mL) and chloroform (50 mL). Crude product was extracted from the aqueous fraction through successive chloroform extractions until no product remained in the aqueous layer. The combined organic extracts were concentrated and purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a CMA:chloroform gradient; 0-30% CMA over 1500 mL, followed by 30% CMA over 1000 mL) to provide 578 mg of N-{3-[4-amino-1-(2-hydroxy-2-methylpropyl)-2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-7-yl]propyl}acetamide as a white semi-solid.

Provenance & Evidence