Water → 3-(3-bromo-2-chlorophenyl)-8-fluoroquinazoline-2,4(1H,3H)-dione

HRID 523272

Reaction equation

HRID 523272 reaction equation
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:15]=1[C:16]([NH:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([Br:25])[C:20]=1[Cl:26])=[O:17].O>C1COCC1>[Br:25][C:21]1[C:20]([Cl:26])=[C:19]([N:18]2[C:16](=[O:17])[C:15]3[C:14](=[C:30]([F:31])[CH:29]=[CH:28][CH:27]=3)[NH:13][C:2]2=[O:4])[CH:24]=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 962WaterHCID 94429TriphosgeneHCID 117761114amino-N-(3-bromo-2-chlorophenyl)-3-fluorobenzamide

Product 1

HCID 1177611123-(3-bromo-2-chlorophenyl)-8-fluoroquinazoline-2,4(1H,3H)-dioneYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triphosgene (453 mg, 1.53 mmol) was added in one portion to a solution of amino-N-(3-bromo-2-chlorophenyl)-3-fluorobenzamide (350 mg, 1.019 mmol) in THF (10 mL) at 0° C. The mixture was stirred at room temperature for 1 h, then was cooled to 0° C. and treated with water until no more gas evolution was observed. The mixture was concentrated and the residue was dissolved in EtOAc, washed sequentially with saturated aqueous NaHCO3, water and brine, and dried and concentrated. The residue was purified by column chromatography on silica gel (24 g), eluting with EtOAc-hexanes (gradient from 0-50%), to provide 3-(3-bromo-2-chlorophenyl)-8-fluoroquinazoline-2,4(1H,3H)-dione as a yellow solid (320 mg, 85% yield). Mass spectrum m/z 369, 371 (M+H)+. 1H NMR (400 MHz, chloroform-d) δ 8.54 (br. s., 1H), 7.97 (d, J=8.1 Hz, 1H), 7.77 (dd, J=6.8, 2.6 Hz, 1H), 7.46 (ddd, J=9.8, 8.3, 1.2 Hz, 1H), 7.36-7.29 (m, 2H), 7.24 (td, J=8.0, 4.8 Hz, 1H).

Workup

  1. temperaturewas cooled to 0° C.
  2. concentrationThe mixture was concentrated
  3. dissolutionthe residue was dissolved in EtOAc
  4. washwashed sequentially with saturated aqueous NaHCO3, water and brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (24 g)
  8. washeluting with EtOAc-hexanes (gradient from 0-50%)

Sources & evidence

ORD record
ord-e2c0956b32fe4fac962701c7e532cfc7
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Linked notes

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