6-Amino-3-chloropyridazine → 6-(2-Fluoro-4-(trifluoromethyl)phenyl)pyridazin-3-amine

HRID 1626440노트

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HRID 1626440 반응식
Cl[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[CH:4][CH:3]=1.[F:9][C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=1B(O)O.[F-].[Cs+].C(N(C(C)C)C(C)C)C>C(O)CC.CCOC(C)=O>[F:9][C:10]1[CH:15]=[C:14]([C:16]([F:17])([F:18])[F:19])[CH:13]=[CH:12][C:11]=1[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[CH:4][CH:3]=1

참가 물질

7

반응물 4

HCID 216436-Amino-3-chloropyridazineHCID 25953Cesium fluorideHCID 81531DiisopropylethylamineHCID 164141452-Fluoro-4-(trifluoromethyl)benzeneboronic acid

생성물 1

HCID 672882866-(2-Fluoro-4-(trifluoromethyl)phenyl)pyridazin-3-amine수율 14.4%

시약·촉매·용매 2

HCID 10311-Propanol용매HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

To a solution of 6-chloropyridazin-3-amine (0.300 g, 2.32 mmol), 2-fluoro-4-(trifluoromethyl)phenylboronic acid (0.626 g, 3.01 mmol), cesium fluoride (0.915 g, 6.02 mmol), and N-ethyl-N-isopropylpropan-2-amine (0.449 g, 3.47 mmol) in propanol (17 ml) degassed with argon was added (dppf)palladium(II) chloride dichloromethane adduct (0.0953 g, 0.116 mmol), and the reaction was heated to 100° C. in a sealed tube for 3 hours. The reaction was cooled to ambient temperature, diluted with EtOAc, and washed with water and saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography on silica gel, eluting with a linear gradient of 0-10% methanol/EtOAc to yield the desired compound (0.086 g, 0.334 mmol, 14.4% yield).

후처리

  1. temperatureThe reaction was cooled to ambient temperature
  2. washwashed with water and saturated sodium chloride
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by flash chromatography on silica gel
  7. washeluting with a linear gradient of 0-10% methanol/EtOAc

출처 및 근거

ORD 기록
ord-d2902e3fe8f74865b1a3efa3b8db0376
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785445B2

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