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

HRID 2416845Notes

Reaction equation

HRID 2416845 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-7d1a12d7bd63455cb9f271597fc76a55
Source dataset
uspto-grants-2004_11
Patent number
US06825199B2

Reaction notes

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