1,3-Dimethyluracil → HCID 71786185, compound

HRID 624592Notes

Reaction equation

HRID 624592 reaction equation
[CH3:1][N:2]1[CH:7]=[CH:6][C:5](=[O:8])[N:4]([CH3:9])[C:3]1=[O:10].[N+:11]([CH2:13]S(C1C=CC(C)=CC=1)(=O)=O)#[C-:12].CC([O-])(C)C.[K+]>CC1OCCC1.CO>[CH3:1][N:2]1[C:7]2=[CH:12][NH:11][CH:13]=[C:6]2[C:5](=[O:8])[N:4]([CH3:9])[C:3]1=[O:10]

Participants

6

Reactant 3

HCID 701221,3-DimethyluracilHCID 161915Tosylmethyl isocyanideHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 71786185HCID 71786185, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 73012-MethyltetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

1,3-Dimethylpyrimidine-2,4(1H,3H)-dione (commercial (40 g, 285 mmol) and 1-(isocyano methylsulfonyl)-4-methylbenzene (commercial) (84 g, 428 mmol) were dissolved in 2-MeTHF (1000 mL) under nitrogen at 30° C. and held for 5 mins. The vessel was then cooled to 0° C. (internal). A solution of KOtBu (commercial) (64.1 g, 571 mmol) in 2-MeTHF (500 mL was 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 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 then 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 (26.34 g, 52%)

Workup

  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 then 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

Sources & evidence

ORD record
ord-f3fbe0564a19439bbaf458390db51f55
Source dataset
uspto-grants-2016_04
Patent number
US09303035B2

Reaction notes

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