4-Chlorobenzoic Acid → 3-(4-Chlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazine

HRID 522879Notes

Reaction equation

HRID 522879 reaction equation
[NH:1]([C:3]1[CH:8]=[N:7][CH:6]=[CH:5][N:4]=1)[NH2:2].[Cl:9][C:10]1[CH:18]=[CH:17][C:13]([C:14](O)=O)=[CH:12][CH:11]=1.[OH-].[NH4+]>>[Cl:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]2[N:4]3[CH:5]=[CH:6][N:7]=[CH:8][C:3]3=[N:1][N:2]=2)=[CH:12][CH:11]=1

Participants

4

Reactant 3

HCID 63184-Chlorobenzoic AcidHCID 14923Ammonium HydroxideHCID 14878232-Hydrazinopyrazine

Product 1

HCID 673767813-(4-Chlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazine

Conditions

Temperature
110 °C

Procedure

To 2-hydrazinopyrazine (1.60 g, 14.55 mmol) was added 4-chloro-benzoic acid (3 eq) followed by 20 mL of polyphosphoric acid, and the reaction mixture was stirred at 110° C. for 18 h. The hot PPA solution was added to ice and neutralized by the addition of ammonium hydroxide (highly exothermic!). The aqueous solution was extracted with ethyl acetate, washed with brine, and dried over anhydrous sodium sulfate. Concentration followed by flash chromatography (silica gel, 1:1 hexanes: ethyl acetate) afforded 3-(4-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazine, as a viscous oil.

Workup

  1. additionThe hot PPA solution was added to ice
  2. extractionThe aqueous solution was extracted with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationConcentration

Sources & evidence

ORD record
ord-24e9a3bbff2040d09a535fde2c205b07
Source dataset
uspto-grants-2016_05
Patent number
US09334269B2

Reaction notes

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