1,3-Dimethyluracil → 1,3-dimethyl-1,6-dihydro-2H-pyrrolo[3,4-d]pyrimidine-2,4(3H)-dione

Temperature

0 °C

1,3-Dimethylpyrimidine-2,4(1H,3H)-dione (commercially available, 40 g, 285 mmol) and toluenesulfonylmethyl isocyanide (commercially available, 84 g, 428 mmol) were dissolved in 2-MeTHF (1000 mL) under nitrogen at 30° C. and held for 5 mins. The vessel was cooled to 0° C. (internal). A solution of KOtBu (commercially available, 64.1 g, 571 mmol) in 2-MeTHF (500 mL was then added to the solution via a dropping funnel over 0.5 h, such that the internal temperature remained below 5° C. On addition of the KOtBu solution, an orange precipitate formed. An additional portion of 2-MeTHF (455 mL) was then charged via dropping funnel over 5 mins. After 40 mins, the dark orange suspension was quenched with sat NH4Cl solution (2×400 mL) charged via dropping funnel over 15 mins. The suspension was diluted with EtOAc (1 L), the layers were separated and the aqueous extracted with EtOAc (3×1 L). The combined organics were dried (MgSO4) and filtered under reduced pressure. The solvent was removed under reduced pressure to afford a brown semi-solid. The solids were suspended in MeOH (300 mL), sonicated and stirred at room temperature for 15 mins, filtered by reduced pressure filtration and washed with MeOH (100 mL). The solid was dried under vacuum at 50° C. for 24 h. The title compound was obtained as a pale brown amorphous solid;

1. customremained below 5° C
2. customan orange precipitate formed
3. customover 5 mins
4. waitAfter 40 mins
5. customthe dark orange suspension was quenched with sat NH4Cl solution (2×400 mL)
6. additioncharged
7. customover 15 mins
8. additionThe suspension was diluted with EtOAc (1 L)
9. customthe layers were separated
10. extractionthe aqueous extracted with EtOAc (3×1 L)
11. dry with materialThe combined organics were dried (MgSO4)
12. filtrationfiltered under reduced pressure
13. customThe solvent was removed under reduced pressure
14. customto afford a brown semi-solid
15. customsonicated
16. filtrationfiltered by reduced pressure filtration
17. washwashed with MeOH (100 mL)
18. customThe solid was dried under vacuum at 50° C. for 24 h

ORD record

ord-676b9e56418145739d1d01aa3f9bc633

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09359381B2