Dichloromethane → 5-Amino-6-(4-fluoro-phenyl)-pyrazine-2-carboxylic acid methyl ester

HRID 1159328Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1159328
Br[C:2]1[N:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.ClCCl.C(N(CC)CC)C.[C]=O.[C:28]([O:31][CH2:32]C)(=[O:30])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].CO>[CH3:32][O:31][C:28]([C:2]1[CH:7]=[N:6][C:5]([NH2:8])=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)[N:3]=1)=[O:30]

Komponenten

8

Edukt 5

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 714639895-Bromo-3-(4-fluorophenyl)pyrazin-2-amineHCID 178418416HCID 178418416, Verbindung

Produkt 1

HCID 675046415-Amino-6-(4-fluoro-phenyl)-pyrazine-2-carboxylic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 887MethanolLösungsmittel

Versuchsvorschrift

To a methanol solution (35 ml) of 5-bromo-3-(4-fluoro-phenyl)-pyrazin-2-ylamine (1.87 g, 6.97 mmol, 1.0 eq) was added 15 ml ethyl acetate at room temperature. [1,1′-bis(diphenylphosphino) ferrocen]palladium(II)chloride 1:1 complex with dichloromethane (0.26 g, 0.32 mmol, 0.05 eq) was added portion-wise to the reaction mixture followed by triethylamine (1.95 ml, 13.5 mmol, 2.0 eq) and the solution was heated with stirring to 110° C. under 70 bar carbon monoxide for 18 hours. On cooling and removal of carbon monoxide, the reaction mixture was concentrated in vacuo and the residue purified by chromatography on silica gel with heptane:ethyl acetate (1:1) to afford 5-Amino-6-(4-fluoro-phenyl)-pyrazine-2-carboxylic acid methyl ester as white crystals. Yield=1.26 g (73%). 1H-NMR (400 MHz, DMSO): δ 3.80 (3H, s), 7.11 (2H, br s), 7.33 (2H, t, J=8.87 Hz), 7.67-7.70 (2H, m), 8.56 (1H, s). HPLC-MS=100%; 1.49 min (MW=247; M+1=248.3).

Aufarbeitung

  1. temperaturethe solution was heated
  2. temperatureOn cooling
  3. customremoval of carbon monoxide
  4. concentrationthe reaction mixture was concentrated in vacuo
  5. customthe residue purified by chromatography on silica gel with heptane:ethyl acetate (1:1)

Quellen und Nachweise

ORD-Eintrag
ord-05adfe0b66324bf09481ecbd04cda547
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07812028B2

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