Water → 2-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

HRID 246098

Reaktionsgleichung

Reaktionsgleichung von HRID 246098
Br[C:2]1[N:3]=[C:4]2[C:10]([CH:11]=[O:12])=[CH:9][N:8]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]2=[N:6][CH:7]=1.[Cl:21][C:22]1[CH:30]=[C:29]2[C:25]([C:26]([Sn](CCCC)(CCCC)CCCC)=[N:27][NH:28]2)=[C:24]([F:44])[CH:23]=1.O.C(=O)(O)[O-].[Na+]>CN(C=O)C.[Cu](I)I.C(OCC)(=O)C>[Cl:21][C:22]1[CH:30]=[C:29]2[C:25]([C:26]([C:2]3[N:3]=[C:4]4[C:10]([CH:11]=[O:12])=[CH:9][N:8]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]4=[N:6][CH:7]=3)=[N:27][NH:28]2)=[C:24]([F:44])[CH:23]=1

Komponenten

8

Edukt 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 578296122-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehydeHCID 178448230HCID 178448230, Verbindung

Produkt 1

HCID 866779472-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehydeAusbeute 47 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 83717Copper iodideKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

2-Bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (7.6 g, 18.6 mmol) and 6-chloro-4-fluoro-3-tributylstannanyl-1H-indazole (crude from Step 3) were dissolved in DMF (180 ml) and purged with Ar gas. Tetrakis(triphenylphosphine)pallladium (1.07 g, 0.93 mmol) and then copper iodide (707 mg, 3.71 mmol) were added and the flask was stoppered and stirred in a 90° C. oil bath for 20 h. The reaction was cooled and water, ethyl acetate and sodium bicarbonate solution were added. The layers were separated, and the aqueous layer was extracted twice more with ethyl acetate. The combined organic layers were washed with water and sodium chloride solution, then dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (methanol/dichloromethane) followed by trituration with diethyl ether/hexanes to give 3.9 g (47%) of 2-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde. (M+H)+=446.

Aufarbeitung

  1. custompurged with Ar gas
  2. temperatureThe reaction was cooled
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted twice more with ethyl acetate
  5. washThe combined organic layers were washed with water and sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. customAfter evaporation
  8. customthe residue was purified by silica gel chromatography (methanol/dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-e28515601bc4484a862ed28efbc7eb4c
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

Verknüpfte Notizen

Wird geladen…