Triphosgene → 3-(3-bromo-2-methylphenyl)-8-fluoroquinazoline-2,4(1H,3H)-dione

HRID 523200Notes

Reaction equation

HRID 523200 reaction equation
[NH2:1][C:2]1[C:18]([F: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].[C:20](=O)(OC(Cl)(Cl)Cl)[O:21]C(Cl)(Cl)Cl.C([O-])(O)=O.[Na+]>C1COCC1.CCOC(C)=O>[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]([F:19])[CH:17]=[CH:16][CH:15]=3)[NH:1][C:20]2=[O:21])[CH:12]=[CH:11][CH:10]=1

Participants

6

Reactant 3

HCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 1076251882-amino-N-(3-bromo-2-methylphenyl)-3-fluorobenzamide

Product 1

HCID 1177612023-(3-bromo-2-methylphenyl)-8-fluoroquinazoline-2,4(1H,3H)-dioneYield 97.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-amino-N-(3-bromo-2-methylphenyl)-3-fluorobenzamide (5.70 g, 17.6 mmol) in THF (100 mL) was treated with bis(trichloromethyl) carbonate (triphosgene) (6.28 g, 21.2 mmol) at room temperature and stirred for 15 min. The mixture was diluted with EtOAc, carefully treated with saturated aqueous NaHCO3 and stirred at room temperature until gas evolution stopped. The separated organic phase was washed sequentially with saturated aqueous NaHCO3, water and brine, and was dried and concentrated. The residue was triturated with ether to provide 3-(3-bromo-2-methylphenyl)-8-fluoroquinazoline-2,4(1H,3H)-dione as an off-white solid (6.00 g, 97% yield). Mass spectrum m/z 349, 351 (M+H)+. 1H NMR (400 MHz, chloroform-d) δ 8.59 (d, J=17.6 Hz, 1H), 7.99 (d, J=8.1 Hz, 1H), 7.70 (dd, J=7.8, 1.2 Hz, 1H), 7.54-7.43 (m, 1H), 7.28-7.21 (m, 2H), 7.21-7.17 (m, 1H), 2.28 (s, 3H).

Workup

  1. stirringstirred at room temperature until gas evolution
  2. washThe separated organic phase was washed sequentially with saturated aqueous NaHCO3, water and brine
  3. customwas dried
  4. concentrationconcentrated
  5. customThe residue was triturated with ether

Sources & evidence

ORD record
ord-30f31b7cd00149ee84cceab6586d4622
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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