Potassium Carbonate → Tert-butyl 7-(5-fluoro-4-methylpyridin-3-yl)-5-methyl-2,6-naphthyridin-3-ylcarbamate

HRID 1502474Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1502474
Cl[C:2]1[N:11]=[C:10]([C:12]2[CH:13]=[N:14][CH:15]=[C:16]([F:19])[C:17]=2[CH3:18])[CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[N:6]=[CH:7]2.[CH3:28]B1OB(C)OB(C)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C(OCC)(=O)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[F:19][C:16]1[C:17]([CH3:18])=[C:12]([C:10]2[CH:9]=[C:8]3[C:3]([CH:4]=[C:5]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[N:6]=[CH:7]3)=[C:2]([CH3:28])[N:11]=2)[CH:13]=[N:14][CH:15]=1

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 86674985Tert-butyl 5-chloro-7-(5-fluoro-4-methylpyridin-3-yl)-2,6-naphthyridin-3-ylcarbamate

Produkt 1

HCID 67976737Tert-butyl 7-(5-fluoro-4-methylpyridin-3-yl)-5-methyl-2,6-naphthyridin-3-ylcarbamateAusbeute 50,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)KatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of tert-butyl 5-chloro-7-(5-fluoro-4-methylpyridin-3-yl)-2,6-naphthyridin-3-ylcarbamate (230 mg, 0.592 mmol), trimethylboroxine (225 mg, 1.78 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (42 mg, 0.059 mmol), and potassium carbonate (165 mg, 1.18 mmol) in dioxane (3 mL) was heated at 100° C. for 2 hours. The reaction mixture was diluted with ethyl acetate (75 mL) and washed with water (50 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue that was purified by flash chromatography (4 g, Silica, 0-100% ethyl acetate in heptane). Desired fractions were combined and evaporated in vacuo to afford the title compound as pale yellow solid (110 mg, 50%), which was used in the next step without further purification.

Aufarbeitung

  1. washwashed with water (50 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide a residue that
  7. customwas purified by flash chromatography (4 g, Silica, 0-100% ethyl acetate in heptane)
  8. customevaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-b934e7be71184e498692d79fd9730134
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09206175B2

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