Sodium hydride → [2-(1,3-Dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrrolo[3,4-d]pyrimidin-6-yl)-ethyl]-carbamic acid tert-butyl ester

1,3-Dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione) (step 1) (4.43 g, 24.72 mmol) and sodium hydride (commercial) (60% dispersion in mineral oil) (1.286 g, 32.1 mmol) were degassed with nitrogen for 15 min. The reagents were then suspended in anhydrous THF (44.5 mL) and stirred for 15 mins at room temperature, then cooled to 0° C. (external). After 10 mins, a solution of tert-butyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (step 2) (6.07 g, 27.2 mmol) in anhydrous THF (44.5 mL) was charged in two portions (2×24 mL). After addition was complete, the ice-bath was removed and the reaction stirred at room temperature for 50 mins. The reaction was then quenched by addition of saturated NH4Cl solution (30 mL). The reaction mixture was diluted with water (30 mL), EtOAc (60 mL) and the layers separated. The aqueous layer was extracted with EtOAc (2×50 mL), saturated with NaCl (s) and extracted with MeCN (4×50 mL). The aqueous layer was evaporated to (˜20 mL) and extracted further with MeCN (3×50 mL). The combined organic layers were dried (Na2SO4) and filtered under reduced pressure and the solvent was evaporated. The resulting solid was adsorbed onto silica and purified via ISCO SiO2 125 g column eluting with 60-95% EtOAc/hexane. The fractions containing product were combined and evaporated to afford a white crystalline solid. The solid was dried under vacuum at 50° C. for 3 h. The title compound was afforded as a white crystalline solid.

1. temperaturecooled to 0° C. (external)
2. waitAfter 10 mins
3. additionAfter addition
4. customthe ice-bath was removed
5. stirringthe reaction stirred at room temperature for 50 mins
6. customThe reaction was then quenched by addition of saturated NH4Cl solution (30 mL)
7. additionThe reaction mixture was diluted with water (30 mL), EtOAc (60 mL)
8. customthe layers separated
9. extractionThe aqueous layer was extracted with EtOAc (2×50 mL), saturated with NaCl (s)
10. extractionextracted with MeCN (4×50 mL)
11. customThe aqueous layer was evaporated to (˜20 mL)
12. extractionextracted further with MeCN (3×50 mL)
13. dry with materialThe combined organic layers were dried (Na2SO4)
14. filtrationfiltered under reduced pressure
15. customthe solvent was evaporated
16. custompurified via ISCO SiO2 125 g column
17. washeluting with 60-95% EtOAc/hexane
18. additionThe fractions containing product
19. customevaporated
20. customto afford a white crystalline solid
21. customThe solid was dried under vacuum at 50° C. for 3 h

ORD record

ord-cb3b2a5c8b8646369c6bfbf69d9487a2

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09303035B2