Methanol → HCID 59006377, compound

HRID 2378961Notes

Reaction equation

HRID 2378961 reaction equation
[N+:1]([C:4]1[C:9]([CH2:10][CH2:11][NH:12][CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)=[CH:8][CH:7]=[CH:6][N:5]=1)([O-])=O.[H][H].C(N(CC)CC)C.[CH3:35][OH:36]>[Pd]>[O:36]=[C:35]1[NH:1][C:4]2[N:5]=[CH:6][CH:7]=[CH:8][C:9]=2[CH2:10][CH2:11][N:12]1[CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 887MethanolHCID 8471Triethylamine3×HCID 59006332HCID 59006332, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 59006377HCID 59006377, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

tert-Butyl 4-(2-(2-nitropyridin-3-yl)ethylamino)piperidine-1-carboxylate (0.561 g, 1.601 mmol) was dissolved in methanol (60 mL). A catalytic amount of 10% palladium on carbon was added to the mixture. Reaction vessel was charged with 2 atm hydrogen gas. Reaction shook at room temperature for 16 hours. The reaction mixture was filtered through a pad of celite twice. Filtrate was concentrated in vacuo. Residue was dissolved in acetonitrile (100 mL). Triethylamine (0.672 ml, 4.82 mmol) was added to the mixture followed by N,N′-carbonyldiimidazole (0.32 g, 1.97 mmol. 1.2 equiv). After 1.5 hours more N,N′-carbonyldiimidazole (0.32 g, 1.97 mmol, 1.2 equiv) was added. Reaction stirred at room temperature for 16 hours. Additional N,N′-carbonyldiimidazole (0.32 g, 1.97 mmol) and triethylamine (0.672 ml, 4.82 mmol) were added and the clear solution was stirred at room temperature for 20 hours. Additional N,N′-carbonyldiimidazole (0.32 g, 1.97 mmol) and triethylamine (350 μL, 251 mmol) were added to the reaction mixture. The clear solution was stirred at room temperature for 68 hours. All solvents were removed by roto-vap. Silica gel chromatography eluting 2M ammonia in methanol-dichloromethane afforded the title compound as off white solid in 92% yield. 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 8.20 (d, J=4.88 Hz, 1 H) 7.92 (s, 1 H) 7.33 (d, J=7.63 Hz, 1 H) 6.82 (dd, J=7.48, 4.73 Hz, 1 H) 4.35-4.50 (m, 1 H) 4.19 (bs, 2 H) 3.37-3.48 (m, 2 H) 2.87-2.92 (m, 2 H) 2.71-2.83 (m, 2 H) 1.72 (d, J=10.38 Hz, 2 H) 1.50-1.63 (m, 2 H) 1.44 (s, 9 H).

Workup

  1. customReaction vessel
  2. customReaction
  3. filtrationThe reaction mixture was filtered through a pad of celite twice
  4. concentrationFiltrate was concentrated in vacuo
  5. dissolutionResidue was dissolved in acetonitrile (100 mL)
  6. customReaction
  7. stirringstirred at room temperature for 16 hours
  8. stirringthe clear solution was stirred at room temperature for 20 hours
  9. stirringThe clear solution was stirred at room temperature for 68 hours
  10. customAll solvents were removed by roto-vap
  11. washSilica gel chromatography eluting 2M ammonia in methanol-dichloromethane

Sources & evidence

ORD record
ord-186bad5f1d9241699f89a56fc754b850
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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