Tri-o-tolylphosphine → 4,6-Diamino-2-propyl-nicotinonitrile

HRID 1364529Notes

Reaction equation

HRID 1364529 reaction equation
Br[C:2]1[N:9]=[C:8]([NH2:10])[CH:7]=[C:6]([NH2:11])[C:3]=1[C:4]#[N:5].[C:12]1(C)[CH:17]=CC=C[C:13]=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[NH2:11][C:6]1[C:3]([C:4]#[N:5])=[C:2]([CH2:13][CH2:12][CH3:17])[N:9]=[C:8]([NH2:10])[CH:7]=1

Participants

5

Reactant 2

HCID 80271Tri-o-tolylphosphineHCID 1706684,6-Diamino-2-bromo-3-pyridinecarbonitrile

Product 1

HCID 193718624,6-Diamino-2-propyl-nicotinonitrileYield 65.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To 5 mg (0.023 mmol) of palladium(II)acetate, 213 mg (1.00 mmol) of 2-bromo-4,6-diaminonicotinonitrile, and 60 mg (0.20 mmol) of tri(o-tolyl)phosphine was added 0.5 mL of DMF. The flask was purged with N2 while stirring, then 5.0 mL of the n-propylzinc iodide solution was via syringe. The mixture was heated at 85° C. for 2.5 hours then cooled. The mixture was poured into a stirred mixture of 20 mL ethyl acetate and 20 mL water, filtered through diatomaceous earth. The filter cake was washed with ethyl acetate (2×5 mL), and the layers were separated. The organic layer was extracted with water (2×20 mL), and brine (1×20 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to an oil. The oil was purified via silica gel chromatography, eluting with 75% ethyl acetate:hexanes to provide 23 mg (13%) of a white solid. 1H NMR (300 MHz, d6-DMSO) δ 6.17 (s, 2H), 6.09 (s, 2H), 5.52 (s, 1H), 2.50 (t, 2H, J=7.6 Hz), 1.62 (m, 2H), 0.90 (t, J=7.3 Hz, 3H); MS (ESI) m/e 177 (M+H)+, 175 (M−H)−.

Workup

  1. customThe flask was purged with N2
  2. custom5.0 mL of the n-propylzinc iodide solution was via syringe
  3. temperaturethen cooled
  4. additionThe mixture was poured into a stirred mixture of 20 mL ethyl acetate and 20 mL water
  5. filtrationfiltered through diatomaceous earth
  6. washThe filter cake was washed with ethyl acetate (2×5 mL)
  7. customthe layers were separated
  8. extractionThe organic layer was extracted with water (2×20 mL), and brine (1×20 mL)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure to an oil
  12. customThe oil was purified via silica gel chromatography
  13. washeluting with 75% ethyl acetate

Sources & evidence

ORD record
ord-9a24111fb4a749d7988e1e8676087da3
Source dataset
uspto-grants-2011_02
Patent number
US07888374B2

Reaction notes

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