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

Temperature

140 °C

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.

1. temperatureUnder ice-cooling
2. temperaturethe reaction solution was cooled to 0° C.
3. extractionThe reaction solution was extracted with chloroform
4. washthe organic layer was washed with a saturated aqueous sodium chloride solution
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationthe filtrate was concentrated under reduced pressure
8. additionTo the resulting residue were added di-tert-butyl dicarbonate (372 mg), 1,4-dioxane (5 ml)
9. stirringa saturated aqueous sodium hydrogencarbonate solution (5 ml), and the resulting mixture was stirred at room temperature for 8 hours
10. additionWater was added to the reaction solution
11. extractionfollowed by extraction with chloroform
12. washThe organic layer was washed with a saturated aqueous sodium chloride solution
13. dry with materialdried over sodium sulfate
14. filtrationfiltered
15. concentrationthe filtrate was concentrated under reduced pressure
16. additionTo the resulting residue was added diethyl ether
17. filtrationfollowed by filtration
18. washthe precipitate was washed with hexane

ORD record

ord-7476d3d249a34174b9eea10eb274fe1a

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07601728B2