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

HRID 279327Notes

Reaction equation

HRID 279327 reaction equation
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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
50 °C

Procedure

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 NH3 in CH3OH (5 mL). Concentration afforded 4-[{N-(2-amino-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(4-methyl-3-nitrobenzyl)piperidine.

Workup

  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=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

Sources & evidence

ORD record
ord-05495a509a514f87bdd97c13c95a9b1c
Source dataset
uspto-grants-2002_03
Patent number
US06362177B1

Reaction notes

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