5-Bromo-6'-chloro-2-fluoro-[3,4']bipyridinyl-3'-ylamine → 6'-Chloro-2-fluoro-5-(4-piperidin-1-ylmethyl-phenyl)-[3,4]bipyridinyl-3'-ylamine

HRID 1888554Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1888554
Br[C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[C:13]([Cl:15])[N:12]=[CH:11][C:10]=2[NH2:16])[C:5]([F:8])=[N:6][CH:7]=1.Br.[N:18]1([CH2:24][C:25]2[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=2)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>C(#N)C.[F-].[K+].O.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>[Cl:15][C:13]1[N:12]=[CH:11][C:10]([NH2:16])=[C:9]([C:4]2[C:5]([F:8])=[N:6][CH:7]=[C:2]([C:28]3[CH:27]=[CH:26][C:25]([CH2:24][N:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)=[CH:30][CH:29]=3)[CH:3]=2)[CH:14]=1

Komponenten

7

Edukt 2

HCID 582665005-Bromo-6'-chloro-2-fluoro-[3,4']bipyridinyl-3'-ylamineHCID 670275164-(Piperidin-1-ylmethyl)phenylboronic acid hydrobromide

Produkt 1

HCID 582668006'-Chloro-2-fluoro-5-(4-piperidin-1-ylmethyl-phenyl)-[3,4]bipyridinyl-3'-ylamineAusbeute 54 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 522689Potassium FluorideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A degassed mixture of 5-bromo-6′-chloro-2-fluoro-[3,4′]bipyridinyl-3′-ylamine (1.35 g, 4.46 mmol), 4-(piperidin-1-ylmethyl)phenylboronic acid hydrobromide (2.28 g, 7.59 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.29 g, 0.35 mmol) in acetonitrile (70 mL) and 1N aqueous potassium fluoride solution (12 mL) was heated under microwave irradiation at 100° C. for 30 minutes. The cooled reaction was diluted with water (100 mL) and extracted with DCM (3×50 mL). The combined organic layer was dried over sodium sulfate, filtered, and evaporated to afford a residue which was purified by flash chromotagraphy (silica, 25 g column, Biotage, 0-10% methanol in (DCM containing 1% 2M ammonia in methanol)) to afford the title compound as a yellow/orange solid (0.95 g, 54%).

Aufarbeitung

  1. customThe cooled reaction
  2. extractionextracted with DCM (3×50 mL)
  3. dry with materialThe combined organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customto afford a residue which
  7. customwas purified by flash chromotagraphy (silica, 25 g column, Biotage, 0-10% methanol in (DCM containing 1% 2M ammonia in methanol))

Quellen und Nachweise

ORD-Eintrag
ord-3d65e52289714f7ea1577fbd7da15351
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08501765B2

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