Sulfuric Acid → tert-Butyl [(3R)-1-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)piperidin-3-yl]carbamate

Participants

Reaction Conditions

Reaction Steps

Under ice-cooling, water (2 ml) and concentrated sulfuric acid (4 ml) were added to tert-butyl {(3R)-1-[5-(2-chlorobenzyl)-7-cyano-1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl]piperidin-3-yl}carbamate (300 mg), and the resulting mixture was stirred at 140° C. After 3 hours, the reaction solution was cooled to 0° C. and adjusted to pH 8 or higher by dropwise addition of a 5N aqueous potassium carbonate solution. The reaction solution was extracted with chloroform and the organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. To the resulting residue were added di-tert-butyl dicarbonate (372 mg), 1,4-dioxane (5 ml) and a saturated aqueous sodium hydrogencarbonate solution (5 ml), and the resulting mixture was stirred at room temperature for 8 hours. Water was added to the reaction solution, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered and the filtrate was concentrated under reduced pressure. To the resulting residue was added diethyl ether, followed by filtration, and the precipitate was washed with hexane to obtain the title compound (200 mg) as a light-yellow solid.

Provenance & Evidence