3-Butyn-2-amine, 2-methyl- → (5-Bromo-2-chloro-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanol

HRID 896091Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 896091
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:25])=[C:6]([C:8]([C:10]2[CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[F:24])=[CH:14][CH:15]=2)=[O:9])[CH:7]=1.NC(C)(C)C#C>CCN(CC)CC.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:25])=[C:6]([CH:8]([C:10]2[CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[F:24])=[CH:14][CH:15]=2)[OH:9])[CH:7]=1

Komponenten

6

Edukt 2

HCID 763193-Butyn-2-amine, 2-methyl-2×HCID 22349591(5-Bromo-2-chloro-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanone

Produkt 1

HCID 22349578(5-Bromo-2-chloro-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanol

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Katalysator2×HCID 178418476HCID 178418476, VerbindungKatalysator2×HCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

(5-Bromo-2-chloro-phenyl)-[6-(2,4-difluoro-phenylamino)-pyridin-3-yl]-methanone (1.5 g; 3.5 mmol) is dissolved in NEt3 (110 ml), 3-amino-3-methyl-1-butyne (1.7 ml; 15.9 mmol), CuI (200 mg; 1 mmol), PdCl2(PPh3)2 (250 mg; 0.35 mmol) added and refluxed for 45 min. Since only small amount of product is formed, more PdCl2(PPh3)2 (500 mg; 0.7 mmol), CuI (500 mg; 2.5 mmol) and 3-amino-3-methyl-1-butyne (2 ml; 18.7 mmol) is added and refluxing continued for 2.5 hours. The reaction mixture is decanted, the solvent evaporated and the residue purified by chromatography (SiO2; toluene/ethanol/NH3conc 95/5/0.2) to yield the title compound as slightly colored foam (730 mg; 48%).

Aufarbeitung

  1. temperaturerefluxed for 45 min
  2. customSince only small amount of product is formed
  3. temperaturerefluxing
  4. customThe reaction mixture is decanted
  5. customthe solvent evaporated
  6. customthe residue purified by chromatography (SiO2; toluene/ethanol/NH3conc 95/5/0.2)

Quellen und Nachweise

ORD-Eintrag
ord-ba33644dc0524c5699d2ada5985d8904
Quelldatensatz
uspto-grants-2005_07
Patentnummer
US06919336B2

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