Hydrochloric Acid → 1-(3-(Tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone

HRID 1056106Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1056106
Br[C:2]1[C:3]([F:18])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:12][C:13]([CH3:16])([CH3:15])[CH3:14])[C:8]([CH3:17])=[N:7]2.C([Sn](CCCC)(CCCC)[C:24]([O:26]CC)=[CH2:25])CCC.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[F-].[Cs+].Cl>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Cu]I>[C:13]([NH:12][C:9]1[C:8]([CH3:17])=[N:7][C:6]2[C:11]([N:10]=1)=[C:2]([C:24](=[O:26])[CH3:25])[C:3]([F:18])=[CH:4][CH:5]=2)([CH3:16])([CH3:15])[CH3:14]

Komponenten

9

Edukt 5

HCID 313Hydrochloric AcidHCID 25953Cesium fluorideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 897819348-bromo-N-(tert-butyl)-7-fluoro-3-methylquinoxalin-2-amine

Produkt 1

HCID 897821331-(3-(Tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanoneAusbeute 91 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A round bottomed flask was charged with 8-bromo-N-(tert-butyl)-7-fluoro-3-methylquinoxalin-2-amine (605a) (4.70 g, 15.06 mmol), tributyl(1-ethoxyvinyl)tin (Sigma-Aldrich) (7.63 mL, 22.58 mmol), Pd2dba3 (Strem Chemicals Inc., 1.38 g, 1.51 mmol), Xphos (Strem Chemicals Inc.) (718 mg, 1.51 mmol), CuI (Strem Chemicals Inc.) (573 mg, 3.01 mmol) and CsF (Sigma-Aldrich) (6.86 g, 45.2 mmol) in dioxane (75 mL). The tube was sealed and heated to 80° C. in an oil bath overnight. LCMS shows enol ether as major product (m/z (ESI, +ve) 304.0 (M+H)+). The reaction mixture was cooled to RT. Concentrated HCl (aq.) (3.14 mL, 37.6 mmol) was added and the mixture stirred at RT for 30 min. The mixture was filtered through Celite and the filter cake was washed with EtOAc and water. The layers were separated and the aq. layer was extracted with EtOAc (2×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was absorbed onto a plug of silica gel and purified by silica gel chromatography (0-50% EtOAc in hexanes) to provide 1-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone (605b) (3.76 g, 13.64 mmol, 91% yield) as a light orange solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.77 (dd, J=9.00, 5.87 Hz, 1H), 7.08 (t, J=9.00 Hz, 1H), 2.70 (s, 3H), 2.49 (s, 3H), 1.52 (s, 9H). 19F NMR (376 MHz, CDCl3) δ ppm −115.38 (s, 1F). m/z (ESI, +ve) 276.1 (M+H)+.

Aufarbeitung

  1. customThe tube was sealed
  2. temperatureThe reaction mixture was cooled to RT
  3. filtrationThe mixture was filtered through Celite
  4. washthe filter cake was washed with EtOAc and water
  5. customThe layers were separated
  6. extractionthe aq. layer was extracted with EtOAc (2×)
  7. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was absorbed onto a plug of silica gel
  11. custompurified by silica gel chromatography (0-50% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-c8cc8e6e08a14e3190074813d15e6489
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394297B2

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