Cesium fluoride → N-[6-[3-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide

HRID 497656

反応式

HRID 497656 の反応式
[CH2:1]([O:8][C:9]1[CH:10]=[C:11](B(O)O)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F-].[Cs+].Cl[C:21]1[CH:29]=[C:28]2[C:24]([C:25]([NH:38][C:39](=[O:43])[CH2:40][CH2:41][CH3:42])=[N:26][N:27]2[CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])=[CH:23][CH:22]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:2]1([CH2:1][O:8][C:9]2[CH:10]=[C:11]([C:21]3[CH:29]=[C:28]4[C:24]([C:25]([NH:38][C:39](=[O:43])[CH2:40][CH2:41][CH3:42])=[N:26][N:27]4[CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:35])[CH3:36])=[CH:23][CH:22]=3)[CH:12]=[CH:13][CH:14]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 25953Cesium fluorideHCID 27343133-Benzyloxy-phenylboronic acidHCID 10406687N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy)methyl]-1H-indazol-3-yl)butanamide

生成物 1

HCID 22319536N-[6-[3-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-indazol-3-yl]butanamide収率 78.5%

試薬・触媒・溶媒 1

HCID 167845palladium(II) acetate触媒

実験手順

930 mg of 3-benzyloxyphenylboronic acid, 1.24 g of caesium fluoride, 31.5 mg of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)diphenyl and 13.5 mg of palladium acetate are successively added to 1 g of N-[6-chloro-1-[[2-(trimethylsilyl)ethoxy)methyl]-1H-indazol-3-yl)butanamide, prepared in Example 25, and the mixture is refluxed for 18 hours. The reaction medium is filtered through a sinter funnel packed with Celite and 75 cm3 of ethyl acetate are added to the filtrate. The organic phase is washed with 25 cm3 of saturated sodium chloride solution, separated out after settling of the phases has taken place, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50° C.). The crude product obtained is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with a cyclohexane/ethyl acetate gradient (90/10 to 75/25 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.); 1.1 g of N-[6-[3-(phenylmethoxy)phenyl]-1-[[2-(trimethylsilyl)ethoxy)methyl]-1H-indazol-3-yl]butanamide are obtained in the form of an oil in a purity of 80%.

後処理

  1. customprepared in Example 25
  2. temperaturethe mixture is refluxed for 18 hours
  3. filtrationThe reaction medium is filtered through a sinter funnel
  4. additionare added to the filtrate
  5. washThe organic phase is washed with 25 cm3 of saturated sodium chloride solution
  6. customseparated out
  7. dry with materialdried over magnesium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness under reduced pressure (2 kPa; 50° C.)
  10. customThe crude product obtained
  11. customis purified by chromatography under an argon pressure of 50 kPa
  12. washon a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with a cyclohexane/ethyl acetate gradient (90/10 to 75/25 by volume)
  13. additionThe fractions containing the expected product
  14. customevaporated under reduced pressure (2 kPa; 50° C.)

出典と根拠

ORDレコード
ord-c826ca481d034835bcc5a9ec083872a8
出典データセット
uspto-grants-2005_09
特許番号
US06949579B2

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