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

HRID 279326

Reaktionsgleichung

Reaktionsgleichung von HRID 279326
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.[OH:31][C:32]1[C:39]([CH3:40])=[CH:38][CH:37]=[CH:36][C:33]=1[CH:34]=O.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]([CH2:34][C:33]2[CH:36]=[CH:37][CH:38]=[C:39]([CH3:40])[C:32]=2[OH:31])[CH2:23][CH2:24]1)=[O:16])=[O:12]

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 5227773-MethylsalicylaldehydeHCID 5003444Sodium cyanoborohydrideHCID 184262024-[[N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine

Produkt 1

HCID 184262754-[[N-(2-amino-4,5-difluorobenzoyl)glycyl]aminomethyl]-1-(2-hydroxy-3-methylbenzyl)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), 2-hydroxy-3-methylbenzaldehyde (0.25 mmol), methanol (1.0 mL), and acetic acid (0.040 mL) was added NaBH3CN (0.40 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. The resulting material was dissolved into ethyl acetate/methanol=5:1 (1 mL), loaded onto Varian™ Si column, eluted off using ethyl acetate/methanol=5:1 (5 mL), and concentrated. The residue was dissolved in methanol (2 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, and washed with CH3OH (5 mL×2). Product was eluted off using 2 N NH3 in CH3OH (5 mL) and concentrated. Preparative TLC afforded 4-[{N-(2-amino-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(2-hydroxy-3-methylbenzyl)piperidine (Compound No. 2106): The purity was determined by RPLC/MS (97%); ESI/MS m/e 447.0 (M++H, C23H28F2N4O3).

Aufarbeitung

  1. temperatureThe mixture was cooled to room temperature
  2. washwashed with CH3OH (5 mL×2)
  3. washProduct was eluted off
  4. concentrationconcentrated
  5. dissolutionThe resulting material was dissolved into ethyl acetate/methanol=5:1 (1 mL)
  6. washeluted off
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in methanol (2 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. washProduct was eluted off
  15. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-38dd18c5656d49bcad999aa7612e8b0e
Quelldatensatz
uspto-grants-2002_03
Patentnummer
US06362177B1

Verknüpfte Notizen

Wird geladen…