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

HRID 279324

Reaktionsgleichung

Reaktionsgleichung von HRID 279324
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.[Br:31][C:32]1[CH:33]=[CH:34][C:35]([O:40][CH2:41][CH3:42])=[C:36]([CH:39]=1)[CH:37]=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]([CH2:37][C:36]2[CH:39]=[C:32]([Br:31])[CH:33]=[CH:34][C:35]=2[O:40][CH2:41][CH3:42])[CH2:23][CH2:24]1)=[O:16])=[O:12]

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 1449015-Bromo-2-ethoxybenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 184262024-[[N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine

Produkt 1

HCID 5089104-[{N-(2-amino-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(5-bromo-2-ethoxybenzyl)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), 5-bromo-2-ethoxybenzaldehyde (0.15 mmol), methanol (1.2 mL), and acetic acid (0.030 mL) was added NaBH3CN (0.25 mmol) in methanol (0.50 mL). The reaction mixture was stirred at 50° C. for 13 h. The mixture was cooled to room temperature, loaded onto Varian™ SCX column, and washed with CH3OH (5 mL×3). Product was eluted off using 2 N NH3 in CH3OH (5 mL) and concentrated. To the resulting material were added dichloromethane (1 mL) and trifluoroacetic acid (TFA) (0.50 mL) and the solution was stirred at room temperature for 10 min. The reaction mixture was concentrated, and 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 (SiO2, ethyl acetate/methanol=10/1) gave 4-[{N-(2-amino-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(5-bromo-2-ethoxybenzyl)piperidine (Compound No. 2052) (10.2 mg, 38%): The purity was determined by RPLC/MS (96%); ESI/MS m/e 539.2 (M++H, C24H29BrF2N4O3).

Aufarbeitung

  1. temperatureThe mixture was cooled to room temperature
  2. washwashed with CH3OH (5 mL×3)
  3. washProduct was eluted off
  4. concentrationconcentrated
  5. additionTo the resulting material were added dichloromethane (1 mL) and trifluoroacetic acid (TFA) (0.50 mL)
  6. stirringthe solution was stirred at room temperature for 10 min
  7. concentrationThe reaction mixture was concentrated
  8. dissolutionthe residue was dissolved in methanol
  9. washwashed with CH3OH (5 mL×2)
  10. washProduct was eluted off
  11. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-b999fcc9697e417ea71b96dd66618cd6
Quelldatensatz
uspto-grants-2002_03
Patentnummer
US06362177B1

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