Triphosgene → HCID 117760855, compound

HRID 523221Notes

Reaction equation

HRID 523221 reaction equation
[NH2:1][C:2]1[CH:18]=[CH:17][C:16]([F:19])=[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](=[CH:18][CH:17]=[C:16]([F:19])[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 107623903HCID 107623903, compound

Product 1

HCID 117760855HCID 117760855, compoundYield 87.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-amino-N-(3-bromo-2-methylphenyl)-5-fluorobenzamide (0.893 g, 2.76 mmol) and triphosgene (0.984 g, 3.32 mmol) in THF (30 mL) was stirred at room temperature for 2 h. The mixture was carefully treated with saturated aqueous NaHCO3 and stirred until gas evolution ceased. The mixture was extracted twice with DCM. The combined organic phases were washed with water, dried and concentrated. The residue was triturated with DCM to give a white solid, isolated by filtration. The filtrate was concentrated and subjected to column chromatography on silica gel (40 g), eluting with EtOAc-hexanes (gradient from 0-80%), to provide additional solid. The two solids were combined to provide 3-(3-bromo-2-methylphenyl)-6-fluoroquinazoline-2,4(1H,3H)-dione as a white solid (845 mg, 87% yield). Mass spectrum m/z 349, 351 (M+H)+.

Workup

  1. extractionThe mixture was extracted twice with DCM
  2. washThe combined organic phases were washed with water
  3. customdried
  4. concentrationconcentrated
  5. customThe residue was triturated with DCM
  6. customto give a white solid
  7. customisolated by filtration
  8. concentrationThe filtrate was concentrated
  9. washeluting with EtOAc-hexanes (gradient from 0-80%)
  10. customto provide additional solid

Sources & evidence

ORD record
ord-317b097a31f44a9781262f7187f2c281
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

Loading…