Acetic Acid → 4-[[N-(2-amino-4,5-difluorobenzoyl)glycyl]aminomethyl]-1-(4-methyl-3-nitrobenzyl)piperidine

HRID 2187837Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2187837
C(OC([NH:8][C:9]1[CH:28]=[C:27]([F:29])[C:26]([F:30])=[CH:25][C:10]=1[C:11]([NH:13][CH2:14][C:15]([NH:17][CH2:18][CH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)=[O:16])=[O:12])=O)(C)(C)C.[CH3:31][C:32]1[CH:39]=[CH:38][C:35]([CH:36]=O)=[CH:34][C:33]=1[N+:40]([O-:42])=[O:41].C(O)(=O)C.[BH3-]C#N.[Na+]>CO>[NH2:8][C:9]1[CH:28]=[C:27]([F:29])[C:26]([F:30])=[CH:25][C:10]=1[C:11]([NH:13][CH2:14][C:15]([NH:17][CH2:18][CH:19]1[CH2:20][CH2:21][N:22]([CH2:36][C:35]2[CH:38]=[CH:39][C:32]([CH3:31])=[C:33]([N+:40]([O-:42])=[O:41])[CH:34]=2)[CH2:23][CH2:24]1)=[O:16])=[O:12]

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 17989983-Nitro-p-tolualdehydeHCID 5003444Sodium cyanoborohydrideHCID 184262024-[[N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine

Produkt 1

HCID 184262824-[[N-(2-amino-4,5-difluorobenzoyl)glycyl]aminomethyl]-1-(4-methyl-3-nitrobenzyl)piperidine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel2×

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a mixture of 4-[{N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl}aminomethyl]piperidine (0.050 mmol), 4-methyl-3-nitrobenzaldehyde (0.25 mmol), methanol (1.2 mL), and acetic acid (0.050 mL) was added NaBH3CN (0.50 mmol) in methanol (1.0 mL). The reaction mixture was stirred at 50° C. overnight. The mixture was cooled to room temperature, loaded onto Varian™ SCX column, and washed with CH3OH (5 mL×2). Product was eluted off using 2 N NH3, in CH3OH (5 mL) and concentrated. The resulting material was dissolved into ethyl acetate/methanol=2/1 (2 mL), loaded onto Varian™ Si column, eluted off using ethyl acetate/methanol=2/1 (6 mL), and concentrated. The residue was dissolved in methanol (1 mL) and 4 N HCl in dioxane (0.50 mL) was added. The solution was stirred at room temperature overnight and concentrated. The residue was dissolved in methanol, loaded onto Varian™ SCX column, washed with CH3OH (5 mL×2), and eluted off using 2 N NH, in CH3OH (5 mL). Concentration afforded 4-[{N-(2-amino-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(4-methyl-3-nitrobenzyl)piperidine.

Aufarbeitung

  1. temperatureThe mixture was cooled to room temperature
  2. washwashed with CH3OH (5 mL×2)
  3. washProduct was eluted off
  4. concentrationin CH3OH (5 mL) and concentrated
  5. dissolutionThe resulting material was dissolved into ethyl acetate/methanol=2/1 (2 mL)
  6. washeluted off
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in methanol (1 mL)
  9. addition4 N HCl in dioxane (0.50 mL) was added
  10. stirringThe solution was stirred at room temperature overnight
  11. concentrationconcentrated
  12. dissolutionThe residue was dissolved in methanol
  13. washwashed with CH3OH (5 mL×2)
  14. washeluted off
  15. concentrationConcentration

Quellen und Nachweise

ORD-Eintrag
ord-031ee89f283b4a769b850c23f245f7ce
Quelldatensatz
uspto-grants-2002_06
Patentnummer
US06410566B1

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