Ethyl orthoformate → N-[2,3-bis(4-methyl-1-piperazinyl)-6-quinoxalinyl]formimidic acid ethyl ester

HRID 437145Notes

Reaction equation

HRID 437145 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([N:12]1[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]1)[C:6]([N:19]1[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]1)=[N:5]2.[CH2:26]([O:28][CH:29](OCC)OCC)[CH3:27]>S(=O)(=O)(O)O.CCCCCC>[CH2:26]([O:28][CH:29]=[N:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([N:12]1[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]1)[C:6]([N:19]1[CH2:20][CH2:21][N:22]([CH3:25])[CH2:23][CH2:24]1)=[N:5]2)[CH3:27]

Participants

5

Reactant 2

HCID 31214Ethyl orthoformateHCID 127470206-Amino-2,3-bis(4-methyl-1-piperazinyl)quinoxaline

Product 1

HCID 12747031N-[2,3-bis(4-methyl-1-piperazinyl)-6-quinoxalinyl]formimidic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 1118Sulfuric AcidCatalystHCID 8058HexaneSolvent

Procedure

A 17.05 g. portion of 6-amino-2,3-bis(4-methyl-1-piperazinyl)quinoxaline (prepared as in Example 1) is thoroughly mixed with 100 ml. of triethylorthoformate, then 5 drops of concentrated sulfuric acid is added with magnetic stirring and the mixture is heated at reflux in an oil bath (145°-150° C.). The solid is dissolved in about 30 minutes but shortly thereafter a yellow solid is precipitated out. Stirring is continued and the mixture allowed to reflux overnight at a distillate temperature of about 75°-80° C. After refluxing for 16 hours the reflux condenser is replaced with a takeoff condenser with a 10 cm. Vigreux column attached and 6.5 ml. of distillate with a boiling point of about 80° C. is collected over a 21/2 hour period. The maximum oil bath temperature over this period of time is 180° C. The reaction mixture is cooled and the liquid layer is decanted from a small amount of insoluble material. The decanted liquid is stripped of solvent by water pump evacuation and the residual oil is triturated with 50 ml. of hexane and heated to boiling on the steam bath to dissolve the oil. The solution is cooled in an ice bath to yield a solid yellow mass. Additional hexane is added and the precipitate is filtered, washed on the filter with hexane, and pressed dry with suction to give 18.5 g. of the product of the example as a yellow solid.

Workup

  1. temperaturethe mixture is heated
  2. temperatureat reflux in an oil bath (145°-150° C.)
  3. dissolutionThe solid is dissolved in about 30 minutes
  4. customshortly thereafter a yellow solid is precipitated out
  5. stirringStirring
  6. temperatureto reflux overnight at a distillate temperature of about 75°-80° C
  7. temperatureAfter refluxing for 16 hours the reflux condenser
  8. customis replaced with a takeoff condenser with a 10 cm
  9. distillationof distillate with a boiling point of about 80° C. is collected over a 21/2 hour period
  10. waitThe maximum oil bath temperature over this period of time is 180° C
  11. temperatureThe reaction mixture is cooled
  12. customthe liquid layer is decanted from a small amount of insoluble material
  13. customthe residual oil is triturated with 50 ml
  14. temperatureof hexane and heated
  15. dissolutionto dissolve the oil
  16. temperatureThe solution is cooled in an ice bath
  17. customto yield a solid yellow mass
  18. filtrationthe precipitate is filtered
  19. washwashed on the
  20. filtrationfilter with hexane
  21. custompressed dry with suction
  22. customto give 18.5 g

Sources & evidence

ORD record
ord-0118a243eedb41209c80f5f6a4c2d19e
Source dataset
uspto-grants-1977_06
Patent number
US04029788

Reaction notes

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