1,1-Dimethylethyl 4-({[(2-fluoro-6-iodo-4-methylphenyl)amino]-carbonyl}amino)-1-piperidinecarboxylate → 1,1-Dimethylethyl 4-(4-fluoro-6-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinecarboxylate

HRID 2061466Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2061466
[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4](I)[C:3]=1[NH:10][C:11]([NH:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1)=[O:12]>[Cl-].[Cl-].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Pd+2].O1CCOCC1>[F:1][C:2]1[C:3]2[NH:10][C:11](=[O:12])[N:13]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[C:4]=2[CH:5]=[C:6]([CH3:8])[CH:7]=1

Komponenten

4

Edukt 1

HCID 596832811,1-Dimethylethyl 4-({[(2-fluoro-6-iodo-4-methylphenyl)amino]-carbonyl}amino)-1-piperidinecarboxylate

Produkt 1

HCID 596832531,1-Dimethylethyl 4-(4-fluoro-6-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinecarboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178478645Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Under an argon atmosphere, a mixture of 1,4-dioxane (3 ml), palladium 1,1′-bis(diphenylphosphino)ferrocene dichloride (10% mol, 0.0623 mmol, ˜x50 mg), NatBuO (2 eq., 1.26 mmol, 121 mg), were sonicated for 10 minutes at room temperature and 1,1-dimethylethyl 4-({[(2-fluoro-6-iodo-4-methylphenyl)amino]carbonyl}amino)-1-piperidine-carboxylate (D3) (1 eq., 0.623 mmol, 300 mg) was added at room temperature and the mixture was refluxed at 80° C. for one overnight. The reaction mixture was cooled to room temperature, poured onto NH4Cl (saturated solution) and the aqueous solution obtained was extracted with ethyl acetate repeatedly; the organics were combined, dried over Na2SO4, filtered and the solvent was evaporated to afford the crude compound (250 mg) that was purified by MDAP to yield the title compound, 30 mg, 11%.

Aufarbeitung

  1. customwere sonicated for 10 minutes at room temperature
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additionpoured onto NH4Cl (saturated solution)
  4. customthe aqueous solution obtained
  5. extractionwas extracted with ethyl acetate repeatedly
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customto afford the crude compound (250 mg) that
  10. customwas purified by MDAP

Quellen und Nachweise

ORD-Eintrag
ord-824456d63d3e48e6a910313350702a1c
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08283364B2

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