Potassium Carbonate → 6-chloro-5-[2-(dimethylamino)pyrimidin-5-yl]-1H-indole-3-carbaldehyde

HRID 338399

Reaktionsgleichung

Reaktionsgleichung von HRID 338399
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][C:3]=1B1OCC(C)(C)CO1.[C:19](=[O:22])([O-])[O-].[K+].[K+].Br[C:26]1[CH:27]=[N:28][C:29]([N:32]([CH3:34])[CH3:33])=[N:30][CH:31]=1>O1CCOCC1.CN(C=O)C.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.Cl[Pd]Cl.[Fe+2]>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:19]=[O:22])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:26]1[CH:27]=[N:28][C:29]([N:32]([CH3:34])[CH3:33])=[N:30][CH:31]=1

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 127353155-Bromo-N,N-dimethylpyrimidin-2-amineHCID 866987336-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole

Produkt 1

HCID 866987386-chloro-5-[2-(dimethylamino)pyrimidin-5-yl]-1H-indole-3-carbaldehydeAusbeute 58,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 6228DimethylformamideLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a solution of 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole (150 mg, 0.57 mmol) in anhydrous 1,4-dioxane (5 mL) and DMF (1 mL) was added N,N-dimethylformiminium chloride (145 mg, 1.13 mmol). The reaction mixture was stirred at room temperature for 20 minutes to give a thick solution. The reaction mixture was then treated with 2N aqueous potassium carbonate (393 mg, 2.85 mmol), 5-bromo-N,N-dimethylpyrimidin-2-amine (115 mg, 0.57 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (50 mg, 0.068 mmol) and degassed with nitrogen for 2 minutes. The reaction mixture was heated to 90° C. for 30 minutes. After cooling to room temperature, the solvents were removed in vacuo and the residue was purified by column chromatography on silica gel (EtOAc/petroleum ether=1:5 to 1:1) to afford 6-chloro-5-[2-(dimethylamino)pyrimidin-5-yl]-1H-indole-3-carbaldehyde (100 mg, 58.3% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 12.25 (s, 1H), 9.92 (s, 1H), 8.40 (s, 2H), 8.36 (s, 1H), 8.01 (s, 1H), 7.69 (s, 1H), 3.15 (s, 6H).

Aufarbeitung

  1. customto give a thick solution
  2. customdegassed with nitrogen for 2 minutes
  3. temperatureThe reaction mixture was heated to 90° C. for 30 minutes
  4. temperatureAfter cooling to room temperature
  5. customthe solvents were removed in vacuo
  6. customthe residue was purified by column chromatography on silica gel (EtOAc/petroleum ether=1:5 to 1:1)

Quellen und Nachweise

ORD-Eintrag
ord-c121c62d56234088a67df93722dbdd3e
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889730B2

Verknüpfte Notizen

Wird geladen…