Potassium Carbonate → Tert-butyl 4-(5-cyanopyridin-2-yl)-3-methylpiperazine-1-carboxylate

HRID 874924Notes

Reaction equation

HRID 874924 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH:10]([CH3:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:16]1[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][N:17]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:20]([C:19]1[CH:22]=[CH:23][C:16]([N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH:10]2[CH3:14])=[N:17][CH:18]=1)#[N:21]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2756810tert-Butyl 3-methylpiperazine-1-carboxylateHCID 51520946-Chloro-3-pyridinecarbonitrile

Product 1

HCID 69935291Tert-butyl 4-(5-cyanopyridin-2-yl)-3-methylpiperazine-1-carboxylateYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

3-Methyl-piperazine-1-carboxylic acid tert-butyl ester (200 mg, 1.0 mmol) was dissolved in dry DMF (10 mL) taken in a shield tube. To the reaction mixture was added 6-chloronicotinonitrile (70 mg, 1.0 mmol) followed by potassium carbonate (140 mg, 1.0 mmol) and the mixture was heated to 150° C. for 3 h. The reaction mixture was cooled to room temperature and the solvent was evaporated under reduced pressure. The product was extracted with EtOAc and the organic layer was washed with H2O and brine and dried over anhydrous sodium sulfate. Solvent was removed under reduced pressure and the crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 30% EtOAc in petroleum ether) to afford compound tert-butyl 4-(5-cyanopyridin-2-yl)-3-methylpiperazine-1-carboxylate (120 mg, yield 40%) as yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.42 (d, J=2.2 Hz, 1H), 7.63 (dd, J=9.0 Hz, J=2.4 Hz, 1H), 6.56 (d, J=9.0 Hz, 1H), 4.53 (m, 1H), 4.13-3.91 (m, 3H), 3.29-3.16 (m, 2H), 3.02 (m, 1H), 1.49 (s, 9H), 1.20 (d, J=6.6 Hz, 3H).

Workup

  1. customtaken in a shield tube
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customthe solvent was evaporated under reduced pressure
  4. extractionThe product was extracted with EtOAc
  5. washthe organic layer was washed with H2O and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customSolvent was removed under reduced pressure
  8. customthe crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 30% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-7d351054961b429e9aabfe349eabf1a9
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

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