1,3-Dibromopropane → 4-[(3-Bromo-propyl)-[1,2,4]triazol-4-yl-amino]-benzonitrile

HRID 19902Notes

Reaction equation

HRID 19902 reaction equation
[H-].[Na+].[N:3]1[N:4]=[CH:5][N:6]([NH:8][C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=2)[CH:7]=1.[Br:17][CH2:18][CH2:19][CH2:20]Br.C(OCC)(=O)C>CS(C)=O>[Br:17][CH2:18][CH2:19][CH2:20][N:8]([N:6]1[CH:5]=[N:4][N:3]=[CH:7]1)[C:9]1[CH:10]=[CH:11][C:12]([C:13]#[N:14])=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 80011,3-DibromopropaneHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 10307909Benzonitrile, 4-(4H-1,2,4-triazol-4-ylamino)-

Product 1

HCID 219768764-[(3-Bromo-propyl)-[1,2,4]triazol-4-yl-amino]-benzonitrile

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Sodium hydride (60%, 240 mg, 6.0 mmol) was added to a solution of 4-([1,2,4]triazol-4-ylamino)-benzonitrile (926 mg, 5.0 mmol) in DMSO (25 mL) at r.t. The mixture was stirred for 1 hour at this temperature and 1,3-dibromopropane (5 mL) was added. The reaction mixture was stirred overnight and ethyl acetate (100 mL) was added. The mixture was transferred into a separation funnel and extracted with water (twice 100 mL) and brine (20 mL). The organic layer was dried over sodium sulphate and concentrated under reduced pressure (water bath temperature <30° C.). The resulting orange oil was mixed with diethyl ether (100 mL) and filtered through a layer of silica (ca. 5 cm). The silica was washed with more diethyl ether (ca. 100 mL) to remove the excess of 1,3-dibromopropane, the crude product was washed from the silica with acetone (120 mL). The acetone solution was concentrated under reduced pressure and the residue was purified by column-chromatography (eluent: ethyl acetate) to give the title compound as a white solid. Yield: 792 mg (52%). 1H-NMR (400 MHz, d6-DMSO) δ=2.01 (tt, J=7.0, 6.6 Hz, 2H), 3.64 (t, J=6.6 Hz, 2H), 3.95 (t, J=7.0 Hz, 2H), 6.62 (d, J=9.0 Hz, 2H), 7.74 (d, J=9.0 Hz, 2H), 9.02 (s, 2H). 13C-NMR (100 MHz, d6-DMSO) δ=30.38, 32.13, 52.72, 103.17, 113.83, 119.74, 134.63, 144.14, 151.65. LRMS (FAB+): 306.0 (100, [M+H]+).

Workup

  1. additionwas added
  2. customThe mixture was transferred into a separation funnel
  3. extractionextracted with water (twice 100 mL) and brine (20 mL)
  4. dry with materialThe organic layer was dried over sodium sulphate
  5. concentrationconcentrated under reduced pressure (water bath temperature <30° C.)
  6. additionThe resulting orange oil was mixed with diethyl ether (100 mL)
  7. filtrationfiltered through a layer of silica (ca. 5 cm)
  8. washThe silica was washed with more diethyl ether (ca. 100 mL)
  9. customto remove the excess of 1,3-dibromopropane
  10. washthe crude product was washed from the silica with acetone (120 mL)
  11. concentrationThe acetone solution was concentrated under reduced pressure
  12. customthe residue was purified by column-chromatography (eluent: ethyl acetate)

Sources & evidence

ORD record
ord-df2d8bfc4ba14ac298f9d7e151e0a27a
Source dataset
uspto-grants-2010_06
Patent number
US07745472B2

Reaction notes

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