Acetic Acid → 27314-97-2

HRID 967295Notes

Reaction equation

HRID 967295 reaction equation
[CH:1]1[CH:9]=[CH:8][C:7]2[C:3](=[N:4][O:5][N+:6]=2[O-:10])[CH:2]=1.C1CC[N:19]2[C:14](=[N:15]CCC2)CC1.N#CN.C(O)(=O)C.CS(O)(=O)=O.C([O-])(=O)C.[Na+]>C(#N)C.O>[CH:1]1[CH:9]=[CH:8][C:7]2[N+:6]([O-:10])=[N:15][C:14]([NH2:19])=[N+:4]([O-:5])[C:3]=2[CH:2]=1

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 6395Methanesulfonic AcidHCID 9864CyanamideHCID 68075BenzofuroxanHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 517045Sodium Acetate

Product 1

HCID 13541351127314-97-2Yield 37%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
20 °C

Procedure

To a stirred mixture containing 9.5 kg (69.8 moles) of benzofuroxan and 21.3 kg (139.9 moles) of DBU was added a solution containing 5.8 kg (138.0 moles) of cyanamide in 2.7 kg of acetonitrile while maintaining the temperature at 15-25° C. After stirring for 67 hours at 20-25° C. the reaction mixture was diluted with 48 kg of acetonitrile and cooled to 0-10° C. To the cooled mixture was added 8.5 kg (141.5 moles) of acetic acid while maintaining the temperature at 5-15° C. After stirring for 46 hours at 5-10° C., the precipitated product was collected by filtration and washed with acetonitrile (2×15 kg). The resulting solid was suspended in 20 kg of water, stirred for 40 minutes, filtered and the filter cake washed with 10 kg of water. The collected solid was resuspended in 20 kg of water, stirred for 45 minutes, filtered and the filter cake washed with 10 kg of water. The solid collected was suspended in 29 kg of water and to the suspension was added 8.7 kg (90.5 moles) of methanesulfonic acid. The mixture was stirred at 40-50° C. until dissolution was complete. The resulting solution was added to a solution containing 9.2 kg (112.2 moles) of sodium acetate in 49 kg of water and stirred at 10-25° C. for 1.5 hours. The precipitated product was collected by filtration and washed with 10 kg of water. The collected product was suspended in 20 kg of water, stirred for 55 minutes, filtered and the filter cake washed with 10 kg of water. The solid collected was resuspended in 20 kg of water, stirred for 55 minutes, filtered and the filter cake washed with 10 kg of water. The product obtained was dried to constant weight at 50-55° C. to give 4.6 kg of tirapazamine.

Workup

  1. additionwas added a solution
  2. temperaturecooled to 0-10° C
  3. temperaturewhile maintaining the temperature at 5-15° C
  4. stirringAfter stirring for 46 hours at 5-10° C.
  5. filtrationthe precipitated product was collected by filtration
  6. washwashed with acetonitrile (2×15 kg)
  7. stirringstirred for 40 minutes
  8. filtrationfiltered
  9. washthe filter cake washed with 10 kg of water
  10. stirringstirred for 45 minutes
  11. filtrationfiltered
  12. washthe filter cake washed with 10 kg of water
  13. customThe solid collected
  14. stirringThe mixture was stirred at 40-50° C. until dissolution
  15. additionThe resulting solution was added to a solution
  16. stirringstirred at 10-25° C. for 1.5 hours
  17. filtrationThe precipitated product was collected by filtration
  18. washwashed with 10 kg of water
  19. stirringstirred for 55 minutes
  20. filtrationfiltered
  21. washthe filter cake washed with 10 kg of water
  22. customThe solid collected
  23. stirringstirred for 55 minutes
  24. filtrationfiltered
  25. washthe filter cake washed with 10 kg of water
  26. customThe product obtained
  27. customwas dried to constant weight at 50-55° C.

Sources & evidence

ORD record
ord-135217acf3b24f22bd38bbd98f8e421e
Source dataset
uspto-grants-2005_10
Patent number
US06953852B2

Reaction notes

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