2,6-Dichloropyrazine → 3-[[(6-Chloro-2-pyrazinyl)amino]methyl]benzonitrile

HRID 2182171Notes

Reaction equation

HRID 2182171 reaction equation
Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([Cl:8])[N:3]=1.[NH2:9][CH2:10][C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][CH:18]=1)[C:14]#[N:15].CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:8][C:4]1[N:3]=[C:2]([NH:15][CH2:14][C:13]2[CH:12]=[C:11]([CH:18]=[CH:17][CH:16]=2)[C:10]#[N:9])[CH:7]=[N:6][CH:5]=1

Participants

7

Reactant 4

HCID 785042,6-DichloropyrazineHCID 457594Benzonitrile, 3-(aminomethyl)-HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxide

Product 1

HCID 224820193-[[(6-Chloro-2-pyrazinyl)amino]methyl]benzonitrileYield 30.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 2,6-dichloropyrazine (75 mg, 0.503 mmol), 3-aminomethyl-benzonitrile (73 mg, 0.553 mmol), sodium t-butoxide (58 mg, 0.604 mmol), BINAP (12.5 mg, 0.020 mmol), and Pd2(dba)3 (9.2 mg, 0.010 mmol) in toluene (2 mL) was heated at reflux under nitrogen for 10 h. The solution was cooled to room temperature and filtered through a celite pad. The celite pad was washed with ethyl acetate several times. The combined filtrate was concentrated in vacuo to give the crude title compound. The product was purified by chromatography (silica, 5% MeOH/dichlormethane) to give 37.6 mg 3-[(6-chloro-pyrazin-2-ylamino)-methyl]-benzonitrile I-4n.

Workup

  1. temperaturewas heated
  2. temperatureat reflux under nitrogen for 10 h
  3. filtrationfiltered through a celite pad
  4. washThe celite pad was washed with ethyl acetate several times
  5. concentrationThe combined filtrate was concentrated in vacuo
  6. customto give the crude title compound
  7. customThe product was purified by chromatography (silica, 5% MeOH/dichlormethane)

Sources & evidence

ORD record
ord-dd8ad94639cc4ecf866fc36749e2ce0d
Source dataset
uspto-grants-2005_05
Patent number
US06894050B2

Reaction notes

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