Piperazine → 6-(Piperazin-1-yl)pyridin-2-amine

HRID 1726368Notes

Reaction equation

HRID 1726368 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][CH:3]=1.[NH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.CC(C)([O-])C.[Na+].O1CCCC1>C1(C)C=CC=C(C)C=1.CC1C=CC=CC=1[P](C1C=CC=CC=1C)([Pd](Cl)(Cl)[P](C1=C(C)C=CC=C1)(C1C=CC=CC=1C)C1C=CC=CC=1C)C1C=CC=CC=1C>[NH2:8][C:6]1[CH:5]=[CH:4][CH:3]=[C:2]([N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[N:7]=1

Participants

7

Reactant 4

HCID 4837PiperazineHCID 8028TetrahydrofuranHCID 2062462-Amino-6-chloropyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 152909766-(Piperazin-1-yl)pyridin-2-amineYield 5.3%

Reagents, catalysts & solvents 2

HCID 178424406HCID 178424406, compoundCatalystHCID 7929M-XyleneSolvent

Procedure

To a solution of 6-chloro-2-pyridinylamine (406 mg, 3.16 mmol) and piperazine (381 mg, 4.42 mmol) in m-xylene (10 ml), were added sodium tert-butoxide (425 mg, 4.42 mmol) and bis-(tri-o-tolylphosphine)palladium(II) dichloride (124 mg, 0.158 mmol). The mixture was heated at reflux under N2 for 24 h. The reaction was cooled down and tetrahydrofuran (THF, 10 ml) added, and the mixture was filtered on a celite pad. The filtrate was evaporated and purified via flash chromatography (CH2Cl2/MeOH/NH4OH) affording 30 mg of 2-amino-6-(piperazin-1-yl)pyridine (intermediate “Ia”) as a tan solid (5% yield). H-NMR (CD3OD): 2.95 (m, 4H), 3.47 (m, 4H), 5.93 (m, 1H), 6.01 (m, 1H), 7.24 (m, 1H). M+=179.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux under N2 for 24 h
  3. temperatureThe reaction was cooled down
  4. filtrationthe mixture was filtered on a celite pad
  5. customThe filtrate was evaporated
  6. custompurified via flash chromatography (CH2Cl2/MeOH/NH4OH)

Sources & evidence

ORD record
ord-93a3e0854ea24bb88a4dcf0d68a94237
Source dataset
uspto-grants-2009_02
Patent number
US07491821B2

Reaction notes

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