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

HRID 133611

Reaktionsgleichung

Reaktionsgleichung von HRID 133611
[BH3-]C#N.[Na+].C(OC([NH:12][C:13]1[CH:32]=[C:31]([F:33])[C:30]([F:34])=[CH:29][C:14]=1[C:15]([NH:17][CH2:18][C:19]([NH:21][CH2:22][CH:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1)=[O:20])=[O:16])=O)(C)(C)C.[OH:35][C:36]1[C:43]([CH3:44])=[CH:42][CH:41]=[CH:40][C:37]=1[CH:38]=O.CO>C(O)(=O)C>[NH2:12][C:13]1[CH:32]=[C:31]([F:33])[C:30]([F:34])=[CH:29][C:14]=1[C:15]([NH:17][CH2:18][C:19]([NH:21][CH2:22][CH:23]1[CH2:24][CH2:25][N:26]([CH2:38][C:37]2[CH:40]=[CH:41][CH:42]=[C:43]([CH3:44])[C:36]=2[OH:35])[CH2:27][CH2:28]1)=[O:20])=[O:16]

Komponenten

6

Edukt 4

HCID 887MethanolHCID 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 176Acetic AcidLösungsmittel

Versuchsvorschrift

NaBH3CN (0.40 mmol) was added to a mixture of 4-[[N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine (0.050 mmol) with 2-hydroxy-3-methylbenzaldehyde (0.25 mmol), methanol (1.0 mL) and acetic acid (0.040 mL). The resulting mixture was stirred at 50 overnight, cooled to room temperature, loaded onto a Varian™ SCX column and washed with methanol (5 mL×2). The obtained crude product was eluted with a 2 M methanol solution of NH3 (5 mL) and concentrated. The residue was dissolved in ethyl acetate/methanol=5:1 (1 mL), loaded onto a Varian™ SCX column, eluted with ethyl acetate/methanol=5:1 (5 mL) and concentrated. The residue was dissolved in methanol (2 mL), and a 4 M dioxane solution of HCl (0.50 mL) was added to the resulting solution. The obtained mixture was stirred at room temperature overnight and concentrated. The residue was dissolved in methanol, loaded onto a Varian™ SCX column and washed with methanol (5 mL×2). The obtained crude product was eluted with a 2 M methanol solution of NH3 (5 mL), concentrated and purified by preparative TLC to thereby provide 4-[[N-(2-amino-4,5-difluorobenzoyl) glycyl]aminomethyl]-1-(2-hydroxy-3-methylbenzyl)piperidine (Compd. No. 2106). The purity was determined by RPLC/MS (97%). ESI/MS m/e 447.0 (M++H, C23H28F2N4O3).

Aufarbeitung

  1. washwashed with methanol (5 mL×2)
  2. customThe obtained crude product
  3. washwas eluted with a 2 M methanol solution of NH3 (5 mL)
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in ethyl acetate/methanol=5:1 (1 mL)
  6. washeluted with ethyl acetate/methanol=5:1 (5 mL)
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in methanol (2 mL)
  9. additiona 4 M dioxane solution of HCl (0.50 mL) was added to the resulting solution
  10. stirringThe obtained mixture was stirred at room temperature overnight
  11. concentrationconcentrated
  12. dissolutionThe residue was dissolved in methanol
  13. washwashed with methanol (5 mL×2)
  14. customThe obtained crude product
  15. washwas eluted with a 2 M methanol solution of NH3 (5 mL)
  16. concentrationconcentrated
  17. custompurified by preparative TLC to thereby provide 4-[[N-(2-amino-4,5-difluorobenzoyl) glycyl]aminomethyl]-1-(2-hydroxy-3-methylbenzyl)piperidine (Compd. No

Quellen und Nachweise

ORD-Eintrag
ord-e5a35b9f0c8b4a909c2b82744cd629fb
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07390830B1

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