Triethylamine → 4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]octane-1-carboxylic acid

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Reaction Steps

To a stirred mixture of 2.00 g (8.84 mmol) of bicyclo[2.2.2]octane-1,4-dicarboxylic acid monoethyl ester, 2.60 g (9.89 mmol) of 5,6-diamino-1,3-dipropyl-1H-pyrimidine-2,4-dione hydrochloride, 5.32 ml (38.1 mmol) of NEt3, and 30 ml anhydrous acetonitrile was added 3.76 g (9.89 mmol) of HATU. The reaction solution was stirred at rt for 1 h. The reaction mixture was concentrated in vacuo and combined with 40-ml EtOAc and 40 ml of 10% citric acid. The aqueous layer was separated and washed twice with 40-ml portions of EtOAc. The combined organic fractions were washed with 20-ml portions of sat'd NaHCO3 and brine and conc'd in vacuo. The resultant solid was combined, in a 200-ml round-bottom flask equipped with a condenser, with a mixture of 35 ml of i-PrOH and 35 ml of 1 N KOH (35 mmol) and heated to reflux. After heating for 1 hour, the reaction solution was conc'd in vacuo, taken up in 40 ml of water, and washed twice with 30-ml portions of CH2Cl2. The aqueous layer was acidified with conc'd HCl and the resultant precipitate collected by suction filtration to give 3.00 g (87% yield) of an off-white solid. (MH+=389.25)

Provenance & Evidence