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

HRID 2270235노트

반응식

HRID 2270235 반응식
[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

참가 물질

5

반응물 2

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

생성물 1

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

시약·촉매·용매 2

HCID 1140Toluene용매HCID 312751,4-Dioxane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-6f75bdf9195f4c478c4436a1a2f00b79
출처 데이터셋
uspto-grants-2001_12
특허 번호
US06331538B1

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