Cesium carbonate → 5-bromo-1-methyl-3-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)pyridin-2(1H)-one

HRID 68441Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 68441
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[CH:10][C:11]([NH2:14])=[N:12][CH:13]=2)[CH2:4][CH2:3]1.Br[C:16]1[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=[C:20]([Br:22])[CH:21]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[Br:22][C:20]1[CH:21]=[C:16]([NH:14][C:11]2[CH:10]=[CH:9][C:8]([N:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)=[CH:13][N:12]=2)[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=1

Komponenten

6

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 223298335-(4-Methylpiperazin-1-yl)pyridin-2-amine

Produkt 1

HCID 592164475-bromo-1-methyl-3-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)pyridin-2(1H)-oneAusbeute 27,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To 5-(4-Methyl-piperazin-1-yl)-pyridin-2-ylamine (1.06 g, 5.53 mmol), 3,5-Dibromo-1-methyl-1H-pyridin-2-one (1.23 g, 4.61 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (400 mg, 0.691 mmol), and cesium carbonate (4.50 g, 13.8 mmol) was added 45 mL 1,4-dioxane and tris(dibenzylidineacetone)dipalladium(0) (422 mg, 0.461 mmol). This was heated in a 120° C. oil bath for 6 hours under argon. This was partitioned between ethylacetate and dilute aqueous sodium bicarbonate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, concentrated in vacuo, and purified by flash chromatography (gradient elution with 2 to 5% methanol/dichloromethane) to yield 5-Bromo-1-methyl-3-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-1H-pyridin-2-one (484 mg, 1.28 mmol). MS (ESI) 380.0 (M+H)+.

Aufarbeitung

  1. customThis was partitioned between ethylacetate and dilute aqueous sodium bicarbonate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. custompurified by flash chromatography (gradient elution with 2 to 5% methanol/dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-6970fe522c37435098525606d0bce66f
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822457B2

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