Water → 8-bromo-7-fluoro-3-methylquinazoline-2,4(1H,3H)-dione

HRID 1055838Notes

Reaction equation

HRID 1055838 reaction equation
[C:1](OC(Cl)(Cl)Cl)(OC(Cl)(Cl)Cl)=O.[NH2:13][C:14]1[C:23]([Br:24])=[C:22]([F:25])[CH:21]=[CH:20][C:15]=1[C:16]([NH:18][CH3:19])=[O:17].[OH2:26]>C(Cl)Cl>[Br:24][C:23]1[C:22]([F:25])=[CH:21][CH:20]=[C:15]2[C:14]=1[NH:13][C:19](=[O:26])[N:18]([CH3:1])[C:16]2=[O:17]

Participants

5

Reactant 3

HCID 962WaterHCID 94429TriphosgeneHCID 897819312-amino-3-bromo-4-fluoro-N-methylbenzamide

Product 1

HCID 897837248-bromo-7-fluoro-3-methylquinazoline-2,4(1H,3H)-dioneYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of tri-phosgene (Aldrich, St. Louis, Mo.; 0.233 g, 0.784 mmol) and 2-amino-3-bromo-4-fluoro-N-methylbenzamide (720a; 0.57 g, 2.30 mmol) in 23 mL anhydrous DCM was fitted with a water-cooled reflux condenser and drying tube, and heated to reflux overnight. LCMS indicated the reaction was about 85% conversion. Additional triphosgene (0.075 g) was added and heating continued for 5 h. The reaction was cooled and concentrated in vacuo to give 8-bromo-7-fluoro-3-methylquinazoline-2,4(1H,3H)-dione (0.63 g, 2.30 mmol, 100% yield) as a light orange solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.89 (1H, s), 8.03 (1H, dd, J=8.8, 5.9 Hz), 7.23 (1H, t, J=8.6 Hz), 3.26 (3H, s). MS (ESI, pos. ion) m/z: 272.9/275.0 (M+1).

Workup

  1. temperaturecooled
  2. temperaturereflux condenser
  3. customdrying tube
  4. temperatureheated
  5. temperatureto reflux overnight
  6. additionAdditional triphosgene (0.075 g) was added
  7. temperatureheating
  8. temperatureThe reaction was cooled
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-722a7ba97c244547b0f7a5f20e4bf9ab
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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