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

HRID 503113노트

반응식

HRID 503113 반응식
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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 8028Tetrahydrofuran용매

반응 조건

온도
50 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-adbafc938e9f4ba1884366025cd4c58c
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07776890B2

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