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

HRID 279325

Reaktionsgleichung

Reaktionsgleichung von HRID 279325
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.[CH2:31]([O:33][C:34]1[CH:35]=[C:36]([CH:39]=[CH:40][C:41]=1[O:42][CH2:43][CH3:44])[CH:37]=O)[CH3:32].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]([CH2:37][C:36]2[CH:39]=[CH:40][C:41]([O:42][CH2:43][CH3:44])=[C:34]([O:33][CH2:31][CH3:32])[CH:35]=2)[CH2:23][CH2:24]1)=[O:16])=[O:12]

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 748473,4-DiethoxybenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 184262024-[[N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine

Produkt 1

HCID 184262144-[{N-(2-amino-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(3,4-diethoxybenzyl)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), 3,4-diethoxybenzaldehyde (0.15 mmol), methanol (1.2 mL), and acetic acid (0.050 mL) was added NaBH3CN (0.25 mmol) in methanol (0.50 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. To the resulting material were added dichloromethane (2 mL) and phenyl isocyanate (0.10 mL) and the solution was stirred at room temperature for 1 h, 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 residue was dissolved in methanol (0.25 mL) and 4 N HCl in dioxane (0.125 mL) was added. The solution was stirred at room temperature overnight and concentrated. The residue was dissolved in methanol, 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 to afford 4-[{N-(2-amino-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(3,4-diethoxybenzyl)piperidine (Compound No. 2065) (21.2 mg, 84%): The purity was determined by RPLC/MS (97%); ESI/MS m/e 505.2 (M++H, C26H34F2N4O4).

Aufarbeitung

  1. temperatureThe mixture was cooled to room temperature
  2. washwashed with CH3OH (5 mL×2)
  3. washProduct was eluted off
  4. concentrationconcentrated
  5. additionTo the resulting material were added dichloromethane (2 mL) and phenyl isocyanate (0.10 mL)
  6. stirringthe solution was stirred at room temperature for 1 h
  7. washwashed with CH3OH (5 mL×2)
  8. washProduct was eluted off
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in methanol (0.25 mL)
  11. addition4 N HCl in dioxane (0.125 mL) was added
  12. stirringThe solution was stirred at room temperature overnight
  13. concentrationconcentrated
  14. dissolutionThe residue was dissolved in methanol
  15. washwashed with CH3OH (5 mL×2)
  16. washProduct was eluted off
  17. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-fb8fb4addae1454b8f8e181ff8a087a7
Quelldatensatz
uspto-grants-2002_03
Patentnummer
US06362177B1

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