Isonicotinic Acid → 1-Tert-butoxycarbonyl-4-(pyridin-4-ylcarbamoyl)piperazine

HRID 49778Notes

Reaction equation

HRID 49778 reaction equation
[N:1]1[CH:6]=[CH:5][C:4](C(O)=O)=[CH:3][CH:2]=1.C([N:12]([CH2:15]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:24])C=CC=CC=1.[C:34]([O:38][C:39]([N:41]1[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1)=[O:40])([CH3:37])([CH3:36])[CH3:35]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:34]([O:38][C:39]([N:41]1[CH2:46][CH2:45][N:44]([C:15](=[O:24])[NH:12][C:4]2[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=2)[CH2:43][CH2:42]1)=[O:40])([CH3:37])([CH3:35])[CH3:36]

Participants

7

Reactant 4

HCID 5922Isonicotinic AcidHCID 8471TriethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 199401P,P-Diphenylphosphinic azide

Product 1

HCID 98395131-Tert-butoxycarbonyl-4-(pyridin-4-ylcarbamoyl)piperazine

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of pyridine-4-carboxylic acid (1.0 g) and triethylamine (1.2 ml) in toluene (20 ml) was added diphenylphosphoryl azide (1.75 ml) at ambient temperature. The resulting mixture was heated to reflux for 30 minutes and cooled to 0° C. To the mixture was added 1-tert-butoxycarbonylpiperazine (1.51 g), and the mixture was allowed to heat to 90° C. for 1 hour. After cooling to ambient temperature, the reaction mixture was taken up into ethyl acetate, washed in turn with water and brine, dried over magnesium sulfate, and evaporated under reduced pressure. The residue was chromatographed on silica gel (150 ml) eluting with 0-7% methanol in dichloromethane. Trituration with a mixture of diisopropyl ether and ethanol gave 1-tert-butoxycarbonyl-4-(pyridin-4-ylcarbamoyl)piperazine (0.66 g).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 30 minutes
  3. temperatureto heat to 90° C. for 1 hour
  4. temperatureAfter cooling to ambient temperature
  5. washwashed in turn with water and brine
  6. dry with materialdried over magnesium sulfate
  7. customevaporated under reduced pressure
  8. customThe residue was chromatographed on silica gel (150 ml)
  9. washeluting with 0-7% methanol in dichloromethane
  10. additionTrituration with a mixture of diisopropyl ether and ethanol

Sources & evidence

ORD record
ord-9af73983acea4e1ea6cc090fbf6c332f
Source dataset
uspto-grants-2004_03
Patent number
US06710043B1

Reaction notes

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