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Cesium carbonate → 2-(2,4-difluorophenoxy)-5-(2,6-difluorophenyl)-6H-pyrido[1,2-b]pyridazin-6-one

HRID 1454966
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HRID 1454966 반응식
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[CH:9][C:10](=[O:20])[C:11]=2[C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=2[F:19])[N:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].[F:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[OH:35]>CN1C(=O)CCC1.CCOC(C)=O.O>[F:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[O:35][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[CH:9][C:10](=[O:20])[C:11]=2[C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=2[F:19])[N:7]=1
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참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 1230512,4-DifluorophenolHCID 575312262-chloro-5-(2,6-difluorophenyl)-6H-pyrido[1,2-b]pyridazin-6-one

생성물 1

HCID 167499382-(2,4-difluorophenoxy)-5-(2,6-difluorophenyl)-6H-pyrido[1,2-b]pyridazin-6-one

시약·촉매·용매 3

HCID 962Water용매
HCID 8857
Ethyl Acetate
용매
HCID 13387N-methyl-2-pyrrolidone용매

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온도
90 °C

실험 절차

To a solution of 2-chloro-5-(2,6-difluorophenyl)-6H-pyrido[1,2-b]pyridazin-6-one (250 mg, 0.85 mmol) and Cs2CO3 (834 mg, 2.56 mmol) in NMP was added 2,4 difluoro phenol (211 mg, 1.7 mmol). The mixture was heated to 90° C. for 2 hrs until the reaction was complete via LCMS analysis. The reaction was cooled to ambient temperature and diluted with EtOAc and H2O. The aqueous layer was washed with EtOAc and the combined organic layers were washed with 1N NaOH, H2O, brine, dried over MgSO4, and concentrated in vacuo. The crude residue was purified via silica gel chromatography (EtOAc/CH2Cl2, MeOH) to yield the title compound.

후처리

  1. temperatureThe reaction was cooled to ambient temperature
  2. washThe aqueous layer was washed with EtOAc
  3. washthe combined organic layers were washed with 1N NaOH, H2O, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified via silica gel chromatography (EtOAc/CH2Cl2, MeOH)

출처 및 근거

ORD 기록
ord-d85f7b9965bf4d05ac4d3644d2fd6d68
출처 데이터셋
uspto-grants-2009_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07482345B2

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