Acetyl chloride → Acetamide, N-(4-amino-5-cyano-6-ethoxy-2-pyridinyl)-

HRID 1364512Notes

Reaction equation

HRID 1364512 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([O:10][CH2:11][CH3:12])[N:5]=[C:4]([NH2:13])[CH:3]=1.[C:14](Cl)(=[O:16])[CH3:15]>N1C=CC=CC=1.O>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([O:10][CH2:11][CH3:12])[N:5]=[C:4]([NH:13][C:14](=[O:16])[CH3:15])[CH:3]=1

Participants

5

Reactant 2

HCID 6367Acetyl chlorideHCID 131498684,6-Diamino-2-ethoxypyridine-3-carbonitrile

Product 1

HCID 11715520Acetamide, N-(4-amino-5-cyano-6-ethoxy-2-pyridinyl)-Yield 50.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

To 50 mg (0.28 mmol) of 4,6-diamino-2-ethoxy-nicotinonitrile dissolved in 1 mL of pyridine was added 60 μL (0.84 mmol) of acetyl chloride. The mixture was stirred at ambient temperature for 2 hours then diluted with 7 mL of water. The precipitate was filtered and washed with 5 mL of water. The supernatant was extracted with ethyl acetate (3×5 mL), then the combined ethyl acetate layers were back extracted with brine (1×5 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to a solid. This was combined with the precipitated product, dissolved in methanol/ethyl acetate, and concentrated. Most of the remaining pyridine was removed by coevaporation with toluene under reduced pressure. The product was purified via silica gel chromatography, eluting with 50% ethyl acetate/hexanes to provide 31 mg (50%) of a white solid. 1H NMR (300 MHz, d6-DMSO) δ 10.73 (s, 1H), 7.17 (s, 1H), 6.88 (s, 2H), 4.32 (q, 2H, J=7.1 Hz), 2.07 (s, 3H), 1.29 (t, 3H, J=7.1 Hz); MS (ESI) m/e=221 (M+H)+, m/e=219 (M−H)−.

Workup

  1. filtrationThe precipitate was filtered
  2. washwashed with 5 mL of water
  3. extractionThe supernatant was extracted with ethyl acetate (3×5 mL)
  4. extractionthe combined ethyl acetate layers were back extracted with brine (1×5 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure to a solid
  8. dissolutiondissolved in methanol/ethyl acetate
  9. concentrationconcentrated
  10. customMost of the remaining pyridine was removed by coevaporation with toluene under reduced pressure
  11. customThe product was purified via silica gel chromatography
  12. washeluting with 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-16b4dd17213f44859f18f1ddcee52a09
Source dataset
uspto-grants-2011_02
Patent number
US07888374B2

Reaction notes

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