Water → 4-(4-Amino-2-fluorobenzyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

HRID 2240249Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2240249
Br[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][C:9]=2[CH2:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18]C(=O)C(F)(F)F)=[CH:14][C:13]=2[F:25])[N:4](S(C2C=CC(C)=CC=2)(=O)=O)[CH:3]=1.[CH3:36][N:37](C=O)C.O.[OH-].[Li+]>C([O-])(=O)C.[Zn+2].C([O-])(=O)C.[Zn].[C-]#N.[Zn+2].[C-]#N.C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].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].C1COCC1>[NH2:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][C:9]2[CH:8]=[CH:7][N:6]=[C:5]3[NH:4][CH:3]=[C:2]([C:36]#[N:37])[C:10]=23)=[C:13]([F:25])[CH:14]=1

Komponenten

11

Edukt 4

HCID 962Water2×HCID 3939Lithium HydroxideHCID 6228DimethylformamideHCID 59304989N-[4-({3-Bromo-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}methyl)-3-fluorophenyl]-2,2,2-trifluoroacetamide

Produkt 1

HCID 593049784-(4-Amino-2-fluorobenzyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

Reagenzien, Katalysatoren, Lösungsmittel 6

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 11192Zinc AcetateKatalysatorHCID 23994ZincKatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

1.70 g (2.98 mmol) of N-[4-({3-bromo-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-methyl)-3-fluorophenyl]-2,2,2-trifluoroacetamide, 219 mg (1.19 mmol) of zinc acetate, 78 mg (1.19 mmol) of zinc dust, 189 mg (1.61 mmol) of zinc cyanide, 50.0 mg (0.09 mmol) of bis(diphenylphosphino)ferrocene and 27.3 mg (0.03 mmol) of tris(dibenzylideneacetone)dipalladium are initially charged. Under argon, a degassed mixture of 17 ml of DMF and 0.17 ml of water is added, and the mixture is heated at 100° C. for 20 hours. 10 ml of water, 8 ml of THF and 1.21 g (50.3 mmol) of lithium hydroxide are added to the crude mixture, which is then stirred at RT for 20 h. The mixture is concentrated a little and extracted with ethyl acetate. The organic phase is dried over sodium sulfate and concentrated under reduced pressure. The product is purified by chromatography on silica gel (mobile phase: dichloromethane:methanol 25:1).

Aufarbeitung

  1. additionis added
  2. concentrationThe mixture is concentrated a little and
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic phase is dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe product is purified by chromatography on silica gel (mobile phase: dichloromethane:methanol 25:1)

Quellen und Nachweise

ORD-Eintrag
ord-d08bfc67665f4cc98d8f379cb6ef4955
Quelldatensatz
uspto-grants-2010_05
Patentnummer
US07723347B2

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