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

HRID 1626440ノート

反応式

HRID 1626440 の反応式
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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 10311-Propanol溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-d2902e3fe8f74865b1a3efa3b8db0376
出典データセット
uspto-grants-2014_07
特許番号
US08785445B2

反応ノート

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