Potassium Fluoride → 5-(4-amino-2-fluorophenyl)-1-methyl-1H-pyrrole-2-carbonitrile

HRID 1591822노트

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HRID 1591822 반응식
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[F:9].[CH3:10][N:11]1[C:15]([C:16]#[N:17])=[CH:14][CH:13]=[C:12]1B(O)O.[F-].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:6][C:5]1[CH:7]=[CH:8][C:2]([C:12]2[N:11]([CH3:10])[C:15]([C:16]#[N:17])=[CH:14][CH:13]=2)=[C:3]([F:9])[CH:4]=1

참가 물질

5

반응물 3

HCID 522689Potassium FluorideHCID 8218484-Bromo-3-fluoroanilineHCID 11708078(5-cyano-1-methyl-1H-pyrrol-2-yl)boronic acid

생성물 1

HCID 160504325-(4-amino-2-fluorophenyl)-1-methyl-1H-pyrrole-2-carbonitrile수율 98%

시약·촉매·용매 1

HCID 9811564Bis(dibenzylideneacetone)palladium촉매

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온도
25 °C

실험 절차

4-Bromo-3-fluoroaniline (0.95 g, 5.0 mmol), 1-methyl-5-cyano-2-pyrroleboronic acid (1.35 g, 9.0 mmol), KF (0.96 g, 16.5 mmol), and Pd2(dba)3 (120 mg, 0.125 mmol) were added to a 50 mL round bottom flask under nitrogen. The flask was sealed and purged with nitrogen for 5 minutes. THF (12.5 mL) was added and the mixture was purged with nitrogen for an additional 5 minutes. A solution of tri-t-butylphosphine (10% wt in hexanes) (0.74 mL, 0.25 mmol) was added via syringe and the mixture was stirred vigorously at 25° C. for 16 hours. The mixture was diluted with 250 mL of EtOAc, filtered through a plug of silica gel, washed with 200 mL of EtOAc and concentrated to give a crude brown/black semi-solid. Purification via Isco chromatography (the Redisep® column, silica, gradient 5%-100% ethyl acetate in hexane) afforded 5-(4-amino-2-fluorophenyl)-1-methyl-1H-pyrrole-2-carbonitrile as a white solid (1.05 g, 98%).

후처리

  1. customThe flask was sealed
  2. custompurged with nitrogen for 5 minutes
  3. additionTHF (12.5 mL) was added
  4. customthe mixture was purged with nitrogen for an additional 5 minutes
  5. additionA solution of tri-t-butylphosphine (10% wt in hexanes) (0.74 mL, 0.25 mmol) was added via syringe
  6. additionThe mixture was diluted with 250 mL of EtOAc
  7. filtrationfiltered through a plug of silica gel
  8. washwashed with 200 mL of EtOAc
  9. concentrationconcentrated
  10. customto give a crude brown/black semi-solid
  11. customPurification via Isco chromatography (the Redisep® column, silica, gradient 5%-100% ethyl acetate in hexane)

출처 및 근거

ORD 기록
ord-f2219bb2c98e4fb2b4debed68b0be904
출처 데이터셋
uspto-grants-2007_11
특허 번호
US07291643B2

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