Triphosgene → HCID 117760794, compound

HRID 523215Notes

Reaction equation

HRID 523215 reaction equation
[NH2:1][C:2]1[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([Br:13])[C:8]=1[CH3:14])=[O:5].Cl[C:21](Cl)([O:23]C(=O)OC(Cl)(Cl)Cl)Cl.C([O-])(O)=O.[Na+]>C1COCC1>[Br:13][C:9]1[C:8]([CH3:14])=[C:7]([N:6]2[C:4](=[O:5])[C:3]3[C:2](=[C:18]([CH3:19])[CH:17]=[CH:16][CH:15]=3)[NH:1][C:21]2=[O:23])[CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 107623999HCID 107623999, compound

Product 1

HCID 117760794HCID 117760794, compoundYield 91.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-amino-N-(3-bromo-2-methylphenyl)-3-methylbenzamide (1.71 g, 5.36 mmol) and triphosgene (2.07 g, 6.96 mmol) in THF (20 mL) was heated at reflux for 1 h. The mixture was cooled on an ice-water bath and treated with saturated aqueous NaHCO3. Stirring was continued until gas evolution ceased. The resulting mixture was extracted 3 times with DCM. The combined organic phases were washed with water, dried and concentrated. The residue was triturated with ether to give a white solid, collected by filtration. A second trituration of the concentrated filtrate gave additional solid, collected by filtration. The filtrate from this was concentrated and purified by column chromatography on silica gel (40 g), eluting with EtOAc-hexanes (gradient from 0-100%), to provide additional solid. The three solids were combined to provide 3-(3-bromo-2-methylphenyl)-8-methylquinazoline-2,4(1H,3H)-dione as a white solid (1.69 g, 91% yield). Mass spectrum m/z 345, 347 (M+H)+. 1H NMR (400 MHz, chloroform-d): δ 8.07 (d, J=7.9 Hz, 1H), 7.70 (dd, J=7.9, 1.3 Hz, 1H), 7.54 (d, J=7.3 Hz, 1H), 7.27-7.17 (m, 3H), 2.41 (s, 3H), 2.28 (s, 3H).

Workup

  1. temperatureat reflux for 1 h
  2. temperatureThe mixture was cooled on an ice-water bath
  3. extractionThe resulting mixture was extracted 3 times with DCM
  4. washThe combined organic phases were washed with water
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was triturated with ether
  8. customto give a white solid
  9. filtrationcollected by filtration
  10. customA second trituration of the concentrated filtrate gave additional solid
  11. filtrationcollected by filtration
  12. concentrationThe filtrate from this was concentrated
  13. custompurified by column chromatography on silica gel (40 g)
  14. washeluting with EtOAc-hexanes (gradient from 0-100%)
  15. customto provide additional solid

Sources & evidence

ORD record
ord-909f49402afc4d6ab96b0a5b9b91446f
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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