Toluene → 6-Chloro-2-(2-furanyl)-3-pyridinamine

HRID 887726Notes

Reaction equation

HRID 887726 reaction equation
[NH2:1][C:2]1[C:3](I)=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1.[O:10]1[CH:14]=[CH:13][CH:12]=[C:11]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>O.C1COCC1>[NH2:1][C:2]1[C:3]([C:11]2[O:10][CH:14]=[CH:13][CH:12]=2)=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 2734357Furan-2-boronic acidHCID 184070436-Chloro-2-iodopyridin-3-amine

Product 1

HCID 593554186-Chloro-2-(2-furanyl)-3-pyridinamineYield 0.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

3-Amino-6-chloro-2-iodopyridine (1.78 g), 2-furanboronic acid (1.17 g), and sodium carbonate (1.11 g) were suspended in a solvent mixture consistent of toluene (23 mL), THF (23 mL) and water (7 mL). The mixture was degassed using subsequent evaporation and flushing with nitrogen (5×) and tetrakis(triphenylphosphine)palladium(0) (808 mg) was added. The reaction mixture was stirred at 90° C. for 7 hours and 14 hours at room temperature. After addition of 2-furanboronic acid (783 mg), the mixture was stirred again for 4 hours at 90° C., then another portion of 2-furanboronic acid (390 mg) was added and the reaction mixture was stirred for 5.5 hours at 90° C. After 15 hours stirring at room temperature, the reaction mixture was quenched with water and extracted 2× with ethyl acetate. The combined organic layer was washed with brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate=3:1, Rf=0.25) to afford 1.26 mg of the title compound of the formula

Workup

  1. customThe mixture was degassed
  2. customevaporation
  3. customflushing with nitrogen (5×) and tetrakis(triphenylphosphine)palladium(0) (808 mg)
  4. additionwas added
  5. additionAfter addition of 2-furanboronic acid (783 mg)
  6. stirringthe mixture was stirred again for 4 hours at 90° C.
  7. additionanother portion of 2-furanboronic acid (390 mg) was added
  8. stirringthe reaction mixture was stirred for 5.5 hours at 90° C
  9. stirringAfter 15 hours stirring at room temperature
  10. customthe reaction mixture was quenched with water
  11. extractionextracted 2× with ethyl acetate
  12. washThe combined organic layer was washed with brine
  13. dry with materialdried over MgSO4
  14. concentrationconcentrated in vacuum
  15. customThe residue was purified by column chromatography (silica 60, hexane/ethyl acetate=3:1, Rf=0.25)

Sources & evidence

ORD record
ord-f34ba94cf2e34fa9a5ec8a2199ee26a3
Source dataset
uspto-grants-2012_08
Patent number
US08247431B2

Reaction notes

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