Trifluoroacetic acid → 2-Hydrazinopyrazine

HRID 1863927Notes

Reaction equation

HRID 1863927 reaction equation
ClC1C=NC=CN=1.NN.[NH:10]([C:12]1[CH:17]=[N:16][CH:15]=[CH:14][N:13]=1)[NH2:11].[F:18][C:19]([F:24])([F:23])[C:20](O)=O.[OH-].[NH4+]>>[NH:10]([C:12]1[CH:17]=[N:16][CH:15]=[CH:14][N:13]=1)[NH2:11].[F:18][C:19]([F:24])([F:23])[C:20]1[N:13]2[CH:14]=[CH:15][N:16]=[CH:17][C:12]2=[N:10][N:11]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 9321HydrazineHCID 14923Ammonium HydroxideHCID 73277ChloropyrazineHCID 14878232-Hydrazinopyrazine

Product 2

HCID 14878232-HydrazinopyrazineHCID 299234623-(Trifluoromethyl)-1,2,4-triazolo(4,3-a)pyrazine

Conditions

Temperature
140 °C

Procedure

A sample of 2-hydrazinopyrazine was prepared from 2-chloropyrazine and hydrazine using a procedure analogous to that described in the literature [P. J. Nelson and K. T. Potts, J. Org. Chem., 27, 3243 (1962)], except that the crude product was extracted into 10% methanol/dichloromethane and filtered, and the filtrate was concentrated and purified by flash chromatography on silica gel, eluting with 100% ethyl acetate followed by 10% methanol in dichloromethane. A mixture of 2-hydrazinopyrazine (820 mg, 7.45 mmol), trifluoroacetic acid (2.55 g, 22.4 mmol), and polyphosphoric acid (10 mL) was heated to 140° C. with stirring for 18 h. The solution was added to ice and neutralized by the addition of ammonium hydroxide. The aqueous solution was extracted three times with ethyl acetate, washed with brine, and dried over anhydrous magnesium sulfate. Concentration followed by flash chromatography (silica gel, 1:1 hexane:ethyl acetate, then 100% ethyl acetate) afforded the title compound as a solid.

Workup

  1. extractionwas extracted into 10% methanol/dichloromethane
  2. filtrationfiltered
  3. concentrationthe filtrate was concentrated
  4. custompurified by flash chromatography on silica gel
  5. washeluting with 100% ethyl acetate
  6. additionThe solution was added to ice
  7. extractionThe aqueous solution was extracted three times with ethyl acetate
  8. washwashed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationConcentration

Sources & evidence

ORD record
ord-c7928d763e7440df84422c431d2f0a39
Source dataset
uspto-grants-2009_12
Patent number
US07625888B2

Reaction notes

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