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

HRID 523212Notes

Reaction equation

HRID 523212 reaction equation
[NH2:1][C:2]1[C:18]([Cl: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>C1COCC1.C(Cl)Cl>[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]([Cl:19])[CH:17]=[CH:16][CH:15]=3)[NH:1][C:20]2=[O:21])[CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 2

HCID 94429TriphosgeneHCID 1076239932-amino-N-(3-bromo-2-methylphenyl)-3-chlorobenzamide

Product 1

HCID 1177608883-(3-bromo-2-methylphenyl)-8-chloroquinazoline-2,4(1H,3H)-dioneYield 95.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-amino-N-(3-bromo-2-methylphenyl)-3-chlorobenzamide (780 mg, 2.30 mmol) in THF (20 mL) was treated with bis(trichloromethyl) carbonate (1.02 g, 3.45 mmol) and the solution stirred at room temperature for 21 h. The mixture was diluted with DCM and washed sequentially with saturated aqueous NaHCO3, water and brine. The organic phase was dried and concentrated. The residue was purified by column chromatography on silica gel (80 g), eluting with EtOAc-hexanes (gradient from 25-50%), to give 3-(3-bromo-2-methylphenyl)-8-chloroquinazoline-2,4(1H,3H)-dione as a white solid (800 mg, 95% yield). Mass spectrum m/z 365, 367 (M+H)+.

Workup

  1. washwashed sequentially with saturated aqueous NaHCO3, water and brine
  2. customThe organic phase was dried
  3. concentrationconcentrated
  4. customThe residue was purified by column chromatography on silica gel (80 g)
  5. washeluting with EtOAc-hexanes (gradient from 25-50%)

Sources & evidence

ORD record
ord-95bfc29491ae433ba745958caa5596f5
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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