Phosgene → 3-Benzyloxy-7-chloro-1-cyclopropyl-6-fluoro-1H-quinazoline-2,4-dione

HRID 2270235Notes

Reaction equation

HRID 2270235 reaction equation
[CH2:1]([O:8][NH:9][C:10](=[O:23])[C:11]1[CH:16]=[C:15]([F:17])[C:14]([Cl:18])=[CH:13][C:12]=1[NH:19][CH:20]1[CH2:22][CH2:21]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:24](Cl)(Cl)=[O:25]>O1CCOCC1.C1(C)C=CC=CC=1>[CH2:1]([O:8][N:9]1[C:10](=[O:23])[C:11]2[C:12](=[CH:13][C:14]([Cl:18])=[C:15]([F:17])[CH:16]=2)[N:19]([CH:20]2[CH2:21][CH2:22]2)[C:24]1=[O:25])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 6371PhosgeneHCID 22632989N-Benzyloxy-4-chloro-2-cyclopropylamino-5-fluoro-benzamide

Product 1

HCID 226328893-Benzyloxy-7-chloro-1-cyclopropyl-6-fluoro-1H-quinazoline-2,4-dioneYield 46.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of N-benzyloxy-4-chloro-2-cyclopropylamino-5-fluoro-benzamide (Example D-3, 3.00 g, 8.96 mmol) in 1,4-dioxane (50 mL) was reacted with a 20% solution of phosgene (7.00 mL, 9.86 mmol) in toluene in a sealed tube. The mixture was heated to reflux for 24 hours, then cooled and quenched with H2O. The mixture was extracted three times with ethyl acetate, the organic layers combined, dried with sodium sulfate, and concentrated. The residue was then purified by column chromatography (silica gel, 1:1 hexanes/ethyl acetate) to provide 1.5 g of the title compound as a solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 24 hours
  3. temperaturecooled
  4. customquenched with H2O
  5. extractionThe mixture was extracted three times with ethyl acetate
  6. dry with materialdried with sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was then purified by column chromatography (silica gel, 1:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-6f75bdf9195f4c478c4436a1a2f00b79
Source dataset
uspto-grants-2001_12
Patent number
US06331538B1

Reaction notes

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