1,2,4-oxadiazolidine-3,5-dione → HCID 22717673, compound

HRID 1582566Notes

Reaction equation

HRID 1582566 reaction equation
[O:1]1[C:5](=[O:6])[NH:4][C:3](=[O:7])[NH:2]1.[CH:8]([N:11]([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)[C:12](Cl)=[O:13])([CH3:10])[CH3:9]>CN(C)C1C=CN=CC=1>[F:21][C:18]1[CH:17]=[CH:16][C:15]([N:11]([CH:8]([CH3:10])[CH3:9])[C:12]([N:2]2[C:3](=[O:7])[NH:4][C:5](=[O:6])[O:1]2)=[O:13])=[CH:20][CH:19]=1

Participants

4

Reactant 2

HCID 3330851,2,4-oxadiazolidine-3,5-dioneHCID 22717692HCID 22717692, compound

Product 1

HCID 22717673HCID 22717673, compoundYield 57.6%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

A 1 L three neck round bottom flask equipped with nitrogen inlet, thermometer and water condenser was charged with dioxanes (400 mL), 1,2,4-oxadiazole-3,5-dione (30 g 0.29 moles, prepared according to Srivastava, P. and Robins, R., J. Med. Chem. 1981, 24, 1172-1177), 4-dimethylaminopyridine (36 g, 0.29 mole), and N-isopropyl-4-flourophenylcarbamoyl chloride (63 g, 0.29 moles) at room temperature. The yellow mixture was heated at reflux for 4 hours. When no starting material was detected by thin layer chromatography, heat was tuned off and mixture was cooled to room temperature. The solvent was removed under reduced pressure and the resulting solids were suspended in ethyl acetate. The mixture was washed with 1N HCl, and the aqueous layer was extracted twice with ethyl acetate. The combined organic solutions were washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The product was crystallized from chlorobutane and hexanes, and filtered to give 47 g (57%) of the title compound as a white solid melting at 94-95° C.

Workup

  1. temperatureThe yellow mixture was heated
  2. temperatureat reflux for 4 hours
  3. temperatureheat
  4. customThe solvent was removed under reduced pressure
  5. washThe mixture was washed with 1N HCl
  6. extractionthe aqueous layer was extracted twice with ethyl acetate
  7. washThe combined organic solutions were washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe product was crystallized from chlorobutane and hexanes
  11. filtrationfiltered

Sources & evidence

ORD record
ord-67e62b13fbc74c6ca221501acbf84a89
Source dataset
uspto-grants-2004_05
Patent number
US06737383B1

Reaction notes

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