Benzo(B)Thiophene-2-Boronic Acid → 3-Benzo[b]thiophen-2-yl-1H-5-indazolecarbonitrile

HRID 1983452ノート

反応式

HRID 1983452 の反応式
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[N:4](C(OC(C)(C)C)=O)[N:3]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[F-].[K+].[S:43]1[C:47](B(O)O)=[CH:46][C:45]2[CH:51]=[CH:52][CH:53]=[CH:54][C:44]1=2>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[S:43]1[C:47]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=3)[NH:4][N:3]=2)=[CH:46][C:45]2[CH:51]=[CH:52][CH:53]=[CH:54][C:44]1=2

参加物

7

反応物 4

HCID 2359Benzo(B)Thiophene-2-Boronic AcidHCID 522689Potassium FluorideHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 22260825tert-Butyl 3-bromo-5-cyano-1H-indazole-1-carboxylate

生成物 1

HCID 222607323-Benzo[b]thiophen-2-yl-1H-5-indazolecarbonitrile収率 57.3%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
50 °C

実験手順

To a solution of 600 mg of tert-butyl 3-bromo-5-cyano-1H-1-indazolecarboxylate produced in Production Example I-14-b in 9 ml tetrahydrofuran were added 21 mg of palladium(II) acetate, 57 mg of 2-(di-tert-butylphosphino)biphenyl, 357 mg of potassium fluoride and 498 mg of 2-benzo[b]thiopheneboronic acid, and the mixture was stirred at 50° C. for 1 hour. After removing the solvent by distillation, the residue was dissolved in 2 ml of methylene chloride. 4 ml of trifluoroacetic acid was added and the mixture was stirred at room temperature for one day. After removing the solvent by distillation, the residue was diluted with 50 ml of ethyl acetate. The mixture was sequentially washed with saturated aqueous sodium hydrogencarbonate solution and brine, dried over anhydrous magnesium sulfate and the solvent was evaporated. The crude product was purified and separated by silica gel column chromatography (ethyl acetate:toluene=1:19), to give 294 mg of the title compound as bright yellow crystals.

後処理

  1. customAfter removing the solvent
  2. distillationby distillation
  3. dissolutionthe residue was dissolved in 2 ml of methylene chloride
  4. addition4 ml of trifluoroacetic acid was added
  5. stirringthe mixture was stirred at room temperature for one day
  6. customAfter removing the solvent
  7. distillationby distillation
  8. additionthe residue was diluted with 50 ml of ethyl acetate
  9. washThe mixture was sequentially washed with saturated aqueous sodium hydrogencarbonate solution and brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customthe solvent was evaporated
  12. customThe crude product was purified
  13. customseparated by silica gel column chromatography (ethyl acetate:toluene=1:19)

出典と根拠

ORDレコード
ord-0e901ddaa8864c569dcd389785a2fbcc
出典データセット
uspto-grants-2009_06
特許番号
US07541376B2

反応ノート

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