Dimethylformamide → 6-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-nicotinonitrile

HRID 425952Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 425952
Br[C:2]1[CH:3]=[C:4]([O:9][CH:10]([C:12]2[C:17]([Cl:18])=[CH:16][CH:15]=[C:14]([F:19])[C:13]=2[Cl:20])[CH3:11])[C:5]([NH2:8])=[N:6][CH:7]=1.[CH3:21][N:22](C=O)C>O.[C-]#N.[C-]#N.[Zn+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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[NH2:8][C:5]1[C:4]([O:9][CH:10]([C:12]2[C:17]([Cl:18])=[CH:16][CH:15]=[C:14]([F:19])[C:13]=2[Cl:20])[CH3:11])=[CH:3][C:2]([C:21]#[N:22])=[CH:7][N:6]=1

Komponenten

7

Edukt 2

HCID 6228DimethylformamideHCID 211114785-Bromo-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine

Produkt 1

HCID 211113376-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-nicotinonitrileAusbeute 97 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of 5-bromo-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-ylamine (5.00 g, 13.15 mmol) in DMF (73 mL) and water (1 mL) was added Zn(CN)2 (4.50 g, 26.3 mmol), Pd2(dba)3 (0.602 g, 0.65 mmol), and DPPF (0.86 g, 1.55 mmol). The mixture was degassed and charged with nitrogen for three time, and then stirred under nitrogen at 100° C. for 3 hr. The reaction solution was partitioned between ethyl acetate and water. The organic layer was washed with a solution of sat. NH4Cl-conc. NH4OH-water (4:1:4), then dried over MgSO4. The crude product was purified on a silica gel column eluting with ethyl acetate-hexanes (1:4) to provide 6-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-nicotinonitrile as a white solid (4.15 g, 97% yield).

Aufarbeitung

  1. customThe mixture was degassed
  2. additioncharged with nitrogen for three time
  3. customThe reaction solution was partitioned between ethyl acetate and water
  4. washThe organic layer was washed with a solution of sat. NH4Cl-conc
  5. dry with materialNH4OH-water (4:1:4), then dried over MgSO4
  6. customThe crude product was purified on a silica gel column
  7. washeluting with ethyl acetate-hexanes (1:4)

Quellen und Nachweise

ORD-Eintrag
ord-d215c3e8ca934425a94d32ac75e0590f
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08106197B2

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