Methane → N'-[2,3-bis(4-methyl-1-piperazinyl)-6-quinoxalinyl]-N,N-dimethylpropionamidine

HRID 437147Notes

Reaction equation

HRID 437147 reaction equation
[CH3:1][N:2]([CH3:7])[C:3](=O)[CH2:4][CH3:5].P(Cl)(Cl)(Cl)=O.[NH2:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[N:20]=[C:19]([N:24]1[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]1)[C:18]([N:31]1[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]1)=[N:17]2.C>C(#N)C.O>[CH3:30][N:27]1[CH2:28][CH2:29][N:24]([C:19]2[C:18]([N:31]3[CH2:32][CH2:33][N:34]([CH3:37])[CH2:35][CH2:36]3)=[N:17][C:16]3[C:21](=[CH:22][CH:23]=[C:14]([N:13]=[C:3]([N:2]([CH3:7])[CH3:1])[CH2:4][CH3:5])[CH:15]=3)[N:20]=2)[CH2:25][CH2:26]1

Participants

7

Reactant 4

HCID 297MethaneHCID 12965Propanamide, N,N-dimethyl-HCID 24813Phosphorus oxychlorideHCID 127470206-Amino-2,3-bis(4-methyl-1-piperazinyl)quinoxaline

Product 1

HCID 21430503N'-[2,3-bis(4-methyl-1-piperazinyl)-6-quinoxalinyl]-N,N-dimethylpropionamidine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Procedure

To a solution of 11.33 g. (0.112 mole) of N,N-dimethylpropionamide in 110 ml. of acetonitrile (dried over molecular sieves) is added 8.3 ml. of phosphorous oxychloride at 5°-10° C. The mixture is stirred at room temperature for 90 minutes. To the resulting yellow solution is added 13.7 g. (0.040 mole) of 6-amino-2,3-bis(4-methyl-1-piperazinyl)quinoxaline (prepared as in Example 1) in several portions with stirring. The mixture is placed in an oil bath at 65° C. and stirred for 16 hours. The reaction mixture is cooled and is poured into 400 ml. of ice plus water, stirred for 10 minutes and filtered. The filtrate is made alkaline to a pH greater than 13 with 5 N sodium hydroxide and extracted with five 100 ml. portions of chloroform. The combined extract is washed with two 100 ml. portions of water, dried over anhydrous potassium carbonate and anhydrous calcium sulfate and stripped of solvent by water pump evacuation to yield a residual oil which is crystallized on standing. The residue formed is recrystallized from 350 ml. of acetonitrile and is filtered and the solid collected is dried in vacuo at 78° C. over phosphorous pentoxide. The yellow solid obtained is dissolved in 160 ml. of hot acetonitrile, treated with activated charcoal, recrystallized by cooling at -10° C. and is filtered and dried as above to give 4.0 g. of yellow solid, m.p. 173°-175° C.

Workup

  1. customat 5°-10° C
  2. additionTo the resulting yellow solution is added 13.7 g
  3. customThe mixture is placed in an oil bath at 65° C.
  4. stirringstirred for 16 hours
  5. temperatureThe reaction mixture is cooled
  6. additionis poured into 400 ml
  7. filtrationfiltered
  8. extractionextracted with five 100 ml
  9. extractionThe combined extract
  10. washis washed with two 100 ml
  11. dry with materialportions of water, dried over anhydrous potassium carbonate and anhydrous calcium sulfate
  12. customto yield a residual oil which
  13. customis crystallized
  14. customThe residue formed
  15. customis recrystallized from 350 ml
  16. filtrationof acetonitrile and is filtered
  17. customthe solid collected
  18. dry with materialis dried in vacuo at 78° C. over phosphorous pentoxide
  19. customThe yellow solid obtained
  20. dissolutionis dissolved in 160 ml
  21. customrecrystallized
  22. temperatureby cooling at -10° C.
  23. filtrationis filtered
  24. customdried as above
  25. customto give 4.0 g

Sources & evidence

ORD record
ord-0dc294f126644e95a1a6b3f4b3be81c6
Source dataset
uspto-grants-1977_06
Patent number
US04029788

Reaction notes

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