1,2-Dichloroethane → HCID 178509915, Verbindung

HRID 1875105Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1875105
[NH2:1][CH2:2][C:3]1[C:4]([F:22])=[C:5]([O:12][C:13]2[CH:14]=[C:15]([CH:18]=[C:19]([Cl:21])[CH:20]=2)[C:16]#[N:17])[C:6]([CH:9]([F:11])[F:10])=[CH:7][CH:8]=1.[Cl:23][C:24]1[N:25]=[CH:26][N:27](COCC[Si](C)(C)C)[C:28]=1[C:29](O)=[O:30].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C([O-])(O)=O.[Na+].C(O)(C(F)(F)F)=O>CN(C=O)C.ClCCl.C(OCC)(=O)C>[Cl:23][C:24]1[N:25]=[CH:26][NH:27][C:28]=1[C:29]([NH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([F:11])[F:10])=[C:5]([O:12][C:13]2[CH:14]=[C:15]([C:16]#[N:17])[CH:18]=[C:19]([Cl:21])[CH:20]=2)[C:4]=1[F:22])=[O:30]

Komponenten

10

Edukt 6

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 684803913-{[3-(Aminomethyl)-6-(difluoromethyl)-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 684855334-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid

Produkt 1

HCID 178509915HCID 178509915, VerbindungAusbeute 30,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of 3-{[3-(aminomethyl)-6-(difluoromethyl)-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.08 g, 0.245 mmol), 4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid (0.068 g, 0.245 mmol), EDC (0.047 g, 0.245 mmol) and HOBT (0.037 g, 0.245 mmol) in DMF (4 ml) was stirred at RT under an atmosphere of nitrogen for 16 h then ethyl acetate (30 mL) and saturated aqueous NaHCO3 solution (30 mL) were added. The organic layer was separated, washed with saturated aqueous NaHCO3 solution (30 mL), water (30 mL), brine (30 mL), dried over MgSO4, filtered and concentrated. A solution of this residue and TFA (0.019 ml, 0.246 mmol) in dichloromethane (10 ml) was stirred at RT under an atmosphere of nitrogen for 16 h. The solvent was removed under vacuum and the resulting oil was purified by Reverse Phase HPLC (MeCN/water+0.1% TFA). The desired compound was washed with saturated aqueous NaHCO3 solution (25 mL) and extracted with ethyl acetate (25 mL). The organic layer was separated, washed with water (25 mL), brine (25 mL), dried over MgSO4, filtered and concentrated to give the title compound (0.034 g, 30%) as a white powder. 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.73 (s, 1H), 7.44-7.63 (m, 3H), 7.27 (d, 2H), 6.92 (t, 1H), 4.70 (s, 2H). LC/MS m/z 453.2 (M−H).

Aufarbeitung

  1. customThe organic layer was separated
  2. washwashed with saturated aqueous NaHCO3 solution (30 mL), water (30 mL), brine (30 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe solvent was removed under vacuum
  7. customthe resulting oil was purified by Reverse Phase HPLC (MeCN/water+0.1% TFA)
  8. washThe desired compound was washed with saturated aqueous NaHCO3 solution (25 mL)
  9. extractionextracted with ethyl acetate (25 mL)
  10. customThe organic layer was separated
  11. washwashed with water (25 mL), brine (25 mL)
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-d5aaa45e075346249a8b06225adec923
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08304419B2

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