1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 57786049, Verbindung

HRID 1628991Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1628991
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9](O)[C:10]1[N:14]([CH2:15][CH2:16][C:17]([O:19]C)=O)[C:13]2[C:21]([N:25]([CH2:28][CH3:29])[CH2:26][CH3:27])=[CH:22][CH:23]=[CH:24][C:12]=2[N:11]=1.C1(P([N:45]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.N12CCCN=C1CCCCC2.Cl.C(N=C=NCCCN(C)C)C>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[C:10]2=[N:11][C:12]3[CH:24]=[CH:23][CH:22]=[C:21]([N:25]([CH2:28][CH3:29])[CH2:26][CH3:27])[C:13]=3[N:14]2[CH2:15][CH2:16][C:17](=[O:19])[NH:45]1

Komponenten

7

Edukt 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 199401P,P-Diphenylphosphinic azideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 68772648HCID 68772648, Verbindung

Produkt 1

HCID 57786049HCID 57786049, VerbindungAusbeute 39 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel2×

Versuchsvorschrift

To a stirred solution of methyl 3-{2-[(2,4-dichlorophenyl)(hydroxy)methyl]-7-(diethylamino)-1H-benzimidazol-1-yl}propanoate (1.00 g, 2.15 mmol) and diphenylphosphoryl azide (1.39 mL, 6.46 mmol) in toluene (11 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (966 μL, 6.46 mol) at room temperature. After 12 h, the reaction mixture was diluted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with a 0-35% ethyl acetate/n-hexane gradient mixture. A solution of the obtained compound was stirred in the presence of 1.9% palladium on fibroin (200 mg) under hydrogen atmosphere at room temperature for 17 h. The catalyst was removed and the filtrate was concentrated in vacuo. The residue was dissolved in tetrahydrofuran (10 mL) and aqueous sodium hydroxide (8 M, 0.5 mL) was added at room temperature. After 15 h, the reaction mixture was concentrated in vacuo. The residue was dissolved in N,N-dimethylformamide (10 mL) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (973 mg, 5.08 mmol) was added at room temperature. After 6 h, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (155 mg, 1.02 mmol) was added. After 2 h, the reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with a 0-35% ethyl acetate/n-hexane gradient mixture to afford the desired product as pale yellow solid (334 mg, 0.801 mmol, 39%).

Aufarbeitung

  1. washwashed with brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography on silica gel eluting with a 0-35% ethyl acetate/n-hexane gradient mixture
  6. customThe catalyst was removed
  7. concentrationthe filtrate was concentrated in vacuo
  8. dissolutionThe residue was dissolved in tetrahydrofuran (10 mL)
  9. additionaqueous sodium hydroxide (8 M, 0.5 mL) was added at room temperature
  10. waitAfter 15 h
  11. concentrationthe reaction mixture was concentrated in vacuo
  12. dissolutionThe residue was dissolved in N,N-dimethylformamide (10 mL)
  13. waitAfter 6 h
  14. waitAfter 2 h
  15. washwashed with water and brine
  16. dry with materialdried over sodium sulfate
  17. filtrationfiltered
  18. concentrationconcentrated in vacuo
  19. customThe residue was purified by column chromatography on silica gel eluting with a 0-35% ethyl acetate/n-hexane gradient mixture

Quellen und Nachweise

ORD-Eintrag
ord-211d8f54ad49495ea9288822e98eac54
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785460B2

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