Sodium Sulfate → 1-Propyl-2-{[2-(2-fluoropyrid-6-yl)-1H-imidazol-1-yl]methyl}-5-cyano-1H-benzimidazole

HRID 1988698Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1988698
C[Al](C)C.[NH2:5][C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=1[NH:14][CH2:15][CH2:16][CH3:17])[C:9]#[N:10].CO[C:20](=O)[CH2:21][N:22]1[CH:26]=[CH:25][N:24]=[C:23]1[C:27]1[N:32]=[C:31]([F:33])[CH:30]=[CH:29][CH:28]=1.S([O-])([O-])(=O)=O.[Na+].[Na+]>ClCCl.C(O)(=O)C.O.CO>[CH2:15]([N:14]1[C:13]2[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][C:6]=2[N:5]=[C:20]1[CH2:21][N:22]1[CH:26]=[CH:25][N:24]=[C:23]1[C:27]1[N:32]=[C:31]([F:33])[CH:30]=[CH:29][CH:28]=1)[CH2:16][CH3:17]

Komponenten

9

Edukt 4

HCID 24436Sodium SulfateHCID 16682925TrimethylaluminumHCID 223802993-Amino-4-(propylamino)benzonitrileHCID 68499258[2-(2-Fluoropyridin-6-yl)-imidazol-1-yl]acetic acid methyl ester

Produkt 1

HCID 98418061-Propyl-2-{[2-(2-fluoropyrid-6-yl)-1H-imidazol-1-yl]methyl}-5-cyano-1H-benzimidazoleAusbeute 36,8 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 176Acetic AcidLösungsmittelHCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

Trimethylaluminum (0.54 mL of 2.0M in toluene, 1.09 mmol) is added dropwise to a solution of 3-Amino-4-propylaminobenzonitrile (152 mg; 0.87 mmol) in dichloromethane (10 mL), and the mixture was stirred at room temperature for 1 hr. A solution of [2-(2-Fluoropyridin-6-yl)-imidazol-1-yl]acetic acid methyl ester (102 mg; 0.43 mmol) in dichloromethane (5 mL) is added all at once, and the mixture heated at reflux for 16 hr. The brown solution is cooled to room temperature and treated dropwise with methanol (1 mL) then water (2 mL) and stirred at room temperature for 15 min. Anhydrous sodium sulfate is added until the gel becomes solid, the mixture is diluted with dichloromethane (100 mL) and filtered through celite. The filtrate is concentrated to give a brown oil which is dissolved in acetic acid (7 mL) and heated at 100° for 72 hr. The mixture is cooled to room temperature and concentrated. The residue is dissolved in ethyl acetate (15 mL), washed with saturated aqueous NaHCO3 (1×50 mL), then brine (1×50 mL), dried (MgSO4), and concentrated, and the residue purified by preparative thin layer chromatography to give 1-n-Propyl-2-{[2-(2-fluoropyrid-6-yl)-1H-imidazol-1-yl]methyl}-5-cyano-1H-benzimidazole as a light brown semi-solid (57 mg).

Aufarbeitung

  1. temperatureheated
  2. temperatureat reflux for 16 hr
  3. temperatureThe brown solution is cooled to room temperature
  4. filtrationfiltered through celite
  5. concentrationThe filtrate is concentrated
  6. customto give a brown oil which
  7. temperatureheated at 100° for 72 hr
  8. temperatureThe mixture is cooled to room temperature
  9. concentrationconcentrated
  10. dissolutionThe residue is dissolved in ethyl acetate (15 mL)
  11. washwashed with saturated aqueous NaHCO3 (1×50 mL)
  12. dry with materialbrine (1×50 mL), dried (MgSO4)
  13. concentrationconcentrated
  14. customthe residue purified by preparative thin layer chromatography

Quellen und Nachweise

ORD-Eintrag
ord-e907234a597d4ce4abd9c8d79a8b0ae1
Quelldatensatz
uspto-grants-2010_01
Patentnummer
US07642267B2

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