Ethyl Acetate → 1-(6-Pyridin-4-ylpyrazin-2-yl)-1H-benzimidazol-6-amine

HRID 2192690Notes

Reaction equation

HRID 2192690 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[C:12]3[CH:13]=[C:14]([NH2:17])[CH:15]=[CH:16][C:11]=3[N:10]=[CH:9]2)[CH:5]=[N:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].C(O[CH2:28][CH3:29])(=O)C>C(O)CC.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:8]1[CH:29]=[CH:28][C:16]([C:2]2[N:7]=[C:6]([N:8]3[C:12]4[CH:13]=[C:14]([NH2:17])[CH:15]=[CH:16][C:11]=4[N:10]=[CH:9]3)[CH:5]=[N:4][CH:3]=2)=[CH:11][CH:12]=1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 582170941-(6-chloropyrazin-2-yl)-1H-benzimidazol-6-amine

Product 1

HCID 582171611-(6-Pyridin-4-ylpyrazin-2-yl)-1H-benzimidazol-6-amine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 22495535HCID 22495535, compoundSolvent

Procedure

Under a nitrogen atmosphere a mixture of 1-(6-chloropyrazin-2-yl)-1H-benzimidazol-6-amine (50 mg, 0.20 mmol), 4-pyridylboronic add (30 mg, 0.24 mmol), tetrakis(triphenylphosphine)palladium(0) (23 mg, 0.02 mmol) in toluene-n-propanol (2 mL, 3:1) was treated with 2M aqueous sodium carbonate solution (0.14 mL, 0.84 mmol). The resulting mixture was stirred vigorously whilst being heated under reflux overnight. Upon cooling, the mixture was diluted with ethyl acetate (10 mL) and washed with H2O (1×10 mL). The aqueous phase was extracted with ethyl acetate (10 mL) and the organic layers combined and washed with 0.5M Na2CO3, brine and then dried (Na2SO4). Removal of solvent fit vacuo then yielded crude product, which was purified by column chromatography using dichloromethane-methanol (98:2-91:9) as eluent to furnish the product (32 mg).

Workup

  1. temperaturewhilst being heated
  2. temperatureunder reflux overnight
  3. temperatureUpon cooling
  4. washwashed with H2O (1×10 mL)
  5. extractionThe aqueous phase was extracted with ethyl acetate (10 mL)
  6. washwashed with 0.5M Na2CO3, brine
  7. dry with materialdried (Na2SO4)
  8. customRemoval of solvent fit vacuo
  9. customthen yielded crude product, which
  10. customwas purified by column chromatography

Sources & evidence

ORD record
ord-b1dacd5d79e947fcb784914733abbeb1
Source dataset
uspto-grants-2012_12
Patent number
US08329737B2

Reaction notes

Loading…