Ethyl Acetate → 939967-94-9

HRID 578753Notes

Reaction equation

HRID 578753 reaction equation
[N:1]1[N:2]2[CH:10]=[CH:9][CH:8]=[C:3]2[C:4]([NH2:7])=[N:5][CH:6]=1.P(Cl)(Cl)(Cl)=O.[C:16](=O)(O)[O-:17].[Na+].C(OCC)(=O)C>CN(C=O)C>[NH2:7][C:4]1[C:3]2=[CH:8][CH:9]=[C:10]([CH:16]=[O:17])[N:2]2[N:1]=[CH:6][N:5]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24813Phosphorus oxychloride2×HCID 516892Sodium Bicarbonate2×HCID 10441749Pyrrolo[2,1-f][1,2,4]triazin-4-amine

Product 1

HCID 59231937939967-94-9

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Pyrrolo[2,1-f][1,2,4]triazin-4-amine (20.5 g, 152 mmol) was dissolved in 150 mL DMF. Under ice cooling, phosphoryl chloride (31.3 mL, 336 mmol) was added dropwise at such a rate that the internal temperature did not rise above 30° C. The mixture was then heated for 2 days at 50° C. After cooling, another portion of phosphoryl chloride (14.2 mL, 152 mmol) was added, and stirring was continued for another 24 h at 50° C. After cooling, the reaction batch was slowly poured into a mixture of 2.0 L saturated aqueous sodium bicarbonate solution and 2.0 L ethyl acetate. Solid sodium bicarbonate was added until gas evolution stopped. The layers were separated, the aqueous layer was extracted with 0.5 L ethyl acetate, and the combined organic phases were dried over sodium sulfate and concentrated. The residue was suspended in 100 mL diisopropyl ether, stirred at room temperature for 10 min and then filtered. The dried residue was stirred in 6 N hydrochloric acid (500 mL) for 1 h at 50° C. and then poured into an ice/water mixture (1000 mL). The mixture was carefully neutralized with solid sodium bicarbonate, stirred for 30 min at room temperature and then filtered again. The residue was washed with water and ligroin to yield 20.6 g (83% of th.) of white crystals which were used in the next step without further purification.

Workup

  1. customdid not rise above 30° C
  2. temperatureAfter cooling
  3. temperatureAfter cooling
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with 0.5 L ethyl acetate
  6. dry with materialthe combined organic phases were dried over sodium sulfate
  7. concentrationconcentrated
  8. stirringstirred at room temperature for 10 min
  9. filtrationfiltered
  10. stirringThe dried residue was stirred in 6 N hydrochloric acid (500 mL) for 1 h at 50° C.
  11. additionpoured into an ice/water mixture (1000 mL)
  12. stirringstirred for 30 min at room temperature
  13. filtrationfiltered again
  14. washThe residue was washed with water and ligroin
  15. customto yield 20.6 g (83% of th.) of white crystals which
  16. customwere used in the next step without further purification

Sources & evidence

ORD record
ord-551b8b3d4c5c4a128d018666e2a3c546
Source dataset
uspto-grants-2015_05
Patent number
US09040691B2

Reaction notes

Loading…