Cesium carbonate → 4-(2-fluoro-4-methylphenylamino)-1,3,8-trimethyl-1H,6H-pyrido[2,3-d]pyridazine-2,5-dione

HRID 15954

반응식

HRID 15954 반응식
[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[NH2:9].C1(P(C2C=CC=CC=2)C2(P(C3C=CC=CC=3)C3C=CC=CC=3)CC=C3C(C=CC=C3)=C2C2C3C(=CC=CC=3)C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:63]1[C:72]2[C:71](=[O:73])[NH:70][N:69]=[C:68]([CH3:74])[C:67]=2[N:66]([CH3:75])[C:65](=[O:76])[C:64]=1[CH3:77]>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:63]1[C:72]2[C:71](=[O:73])[NH:70][N:69]=[C:68]([CH3:74])[C:67]=2[N:66]([CH3:75])[C:65](=[O:76])[C:64]=1[CH3:77]

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 679842-Fluoro-4-methylanilineHCID 666733724-chloro-1,3,8-trimethyl-1H,6H-pyrido[2,3-d]pyridazine-2,5-dioneHCID 86595863(+/-)-2,2-Bis(diphenylphosphino)-1,1-binaphthyl

생성물 1

HCID 576369294-(2-fluoro-4-methylphenylamino)-1,3,8-trimethyl-1H,6H-pyrido[2,3-d]pyridazine-2,5-dione

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

2-Fluoro-4-methylphenylamine (1.10 equivalents), palladium (II) acetate (0.10 equivalents), rac-2,2-bis(diphenylphosphino)-1,1′-binaphthyl (0.15 equivalents), and cesium carbonate (1.50 equivalents) are added to a solution of 4-chloro-1,3,8-trimethyl-1H,6H-pyrido[2,3-d]pyridazine-2,5-dione (1.00 equivalent) in toluene in a sealed vial. After stirring 10 minutes, the mixture is heated to 80° C. After 24 hours, the reaction mixture is cooled to room temperature and diluted with EtOAc. The resulting precipitate is filtered and washed with EtOAc. The filtrate is diluted with EtOAc and washed with water. The aqueous layer is reextracted with EtOAc. The combined organic layers are washed with brine, dried (Na2SO4) and concentrated. Purification by flash column chromatography gives the desired product.

후처리

  1. waitAfter 24 hours
  2. temperaturethe reaction mixture is cooled to room temperature
  3. filtrationThe resulting precipitate is filtered
  4. washwashed with EtOAc
  5. additionThe filtrate is diluted with EtOAc
  6. washwashed with water
  7. washThe combined organic layers are washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customPurification by flash column chromatography

출처 및 근거

ORD 기록
ord-ac4da3a781684744ac00ba4f98539037
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07732616B2

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