Phenol → 4,6-Diamino-2-phenoxy-3-pyridinecarbonitrile

HRID 1364515Notes

Reaction equation

HRID 1364515 reaction equation
[H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Br[C:11]1[N:18]=[C:17]([NH2:19])[CH:16]=[C:15]([NH2:20])[C:12]=1[C:13]#[N:14]>O1CCOCC1>[NH2:20][C:15]1[C:12]([C:13]#[N:14])=[C:11]([O:9][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[N:18]=[C:17]([NH2:19])[CH:16]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 1706684,6-Diamino-2-bromo-3-pyridinecarbonitrile

Product 1

HCID 214899464,6-Diamino-2-phenoxy-3-pyridinecarbonitrile

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
190 °C

Procedure

A heavy walled, sealable tube suitable for microwave heating was charged with 60 mg (1.5 mmol) of NaH (60% dispersion in mineral oil) and 3 mL of dioxane. To the suspension was added 150 mg (1.59 mmol) of phenol, then the mixture was stirred for 15 min. Next, 212 mg (1.00 mmol) of 2-bromo-4,6-diaminonicotinonitrile was added. The tube was sealed, and the mixture was heated with a microwave apparatus at 190° C. for 25 minutes then cooled and concentrated under reduced pressure. The residue was diluted with 10 mL of toluene and concentrated again under reduced pressure. The remaining material was taken up in 20 mL of ethyl acetate and extracted with 2M NaOH(aq.) (3×5 mL), and brine (1×5 mL), draining some red precipitate with the aqueous layers. The organic layer was dried over MgSO4, filtered, and concentrated to 178 mg (79%) of an orange solid. The product could be further purified via silica gel chromatography, eluting with 50:50 ethyl acetate:hexanes to provide a white solid. 1H NMR (300 MHz, d6-DMSO) δ 7.38 (m, 2H), 7.17 (m, 1H), 7.10 (m, 2H), 6.37 (s, 2H), 6.25 (s, 2H), 5.41 (s, 1H); MS (ESI) m/e=227 (M+H)+, 225 (M−H)−.

Workup

  1. temperatureA heavy walled, sealable tube suitable for microwave heating
  2. customThe tube was sealed
  3. temperaturethen cooled
  4. concentrationconcentrated under reduced pressure
  5. additionThe residue was diluted with 10 mL of toluene
  6. concentrationconcentrated again under reduced pressure
  7. extractionextracted with 2M NaOH(aq.) (3×5 mL), and brine (1×5 mL)
  8. dry with materialThe organic layer was dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated to 178 mg (79%) of an orange solid
  11. customThe product could be further purified via silica gel chromatography
  12. washeluting with 50:50 ethyl acetate
  13. customhexanes to provide a white solid

Sources & evidence

ORD record
ord-7ce5c90e5bbd4c3382441b60d7b3423a
Source dataset
uspto-grants-2011_02
Patent number
US07888374B2

Reaction notes

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