Hydrochloric Acid → 6-Chloro-2-(4-cyclopropyl-1-piperazinyl)-pyrazine hydrochloride

HRID 261064Notes

Reaction equation

HRID 261064 reaction equation
[CH:1]1([N:4]2[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]2)[CH2:3][CH2:2]1.[Cl:10][C:11]1[CH:16]=[N:15][CH:14]=[C:13]([Cl:17])[N:12]=1.Cl>FC(F)(F)CO.C(O)C.C(O)(C)C>[ClH:10].[Cl:17][C:13]1[N:12]=[C:11]([N:7]2[CH2:8][CH2:9][N:4]([CH:1]3[CH2:3][CH2:2]3)[CH2:5][CH2:6]2)[CH:16]=[N:15][CH:14]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 785042,6-DichloropyrazineHCID 47420041-Cyclopropylpiperazine

Product 1

HCID 203960046-Chloro-2-(4-cyclopropyl-1-piperazinyl)-pyrazine hydrochlorideYield 36.1%

Reagents, catalysts & solvents 2

HCID 64092,2,2-TrifluoroethanolSolventHCID 22179027Isopropanol ethanolSolvent

Procedure

Crude N-cyclopropylpiperazine (2.8 g) and 2,6-dichloropyrazine (3.0 g) are combined in 5 ml 2,2,2-trifluoroethanol and the mixture refluxed 4 hours under N2. The mixture is concentrated under vacuum and the residue partitioned between aqueous sodium carbonate and methylene chloride. The combined methylene chloride extracts are extracted with dilute hydrochloric acid which is made basic with sodium hydroxide. The crude base is extracted with methylene chloride and chromatographed on silica gel. Elution with CHCl3 gives fractions containing 2.4 g pure title base which is treated with hydrogen chloride in ethanol-isopropanol to give 2.0 g of the title salt, mp greater than 340° C. with decomposition at 245° C.

Workup

  1. temperaturethe mixture refluxed 4 hours under N2
  2. concentrationThe mixture is concentrated under vacuum
  3. customthe residue partitioned between aqueous sodium carbonate and methylene chloride
  4. extractionThe combined methylene chloride extracts are extracted with dilute hydrochloric acid which
  5. extractionThe crude base is extracted with methylene chloride
  6. customchromatographed on silica gel
  7. washElution with CHCl3
  8. customgives fractions

Sources & evidence

ORD record
ord-ec0c6b84233c4a05821a31509b43171e
Source dataset
uspto-grants-1979_08
Patent number
US04163849

Reaction notes

Loading…