Ammonia → HCID 70443569, compound

HRID 543767Notes

Reaction equation

HRID 543767 reaction equation
[F:1][C:2]([F:22])([F:21])[CH2:3][N:4]=[C:5]([NH2:20])[NH:6][C:7]1[N:12]=[C:11]([S:13][CH2:14][CH2:15][CH2:16][C:17](O)=[O:18])[CH:10]=[N:9][CH:8]=1.ClC(OCC)=O.[NH3:29].[C:30]([OH:37])(=[O:36])/[CH:31]=[CH:32]\[C:33]([OH:35])=[O:34]>C1COCC1.CCOC(C)=O.CCO.C(N(CC)CC)C>[C:30]([OH:37])(=[O:36])/[CH:31]=[CH:32]\[C:33]([OH:35])=[O:34].[F:1][C:2]([F:22])([F:21])[CH2:3][N:4]=[C:5]([NH2:20])[NH:6][C:7]1[N:12]=[C:11]([S:13][CH2:14][CH2:15][CH2:16][C:17]([NH2:29])=[O:18])[CH:10]=[N:9][CH:8]=1

Participants

9

Reactant 4

HCID 222AmmoniaHCID 10928Ethyl chloroformateHCID 444266Maleic AcidHCID 20202781HCID 20202781, compound

Product 1

HCID 70443569HCID 70443569, compoundYield 30%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a suspension of 4-[6-(2-[2,2,2-trifluoroethyl]guanidino)pyrazin-2-ylthio]butyric acid (0.25 g.) in THF (10 ml) at 0° was added triethylamine (0.082 g.), followed by ethyl chloroformate (0.088 g.) and the mixture was stirred for 30 minutes. A solution of ammonia in THF (5 ml.) was added and the mixture stirred again for 30 minutes, the temperature being allowed to rise to room temperature. The mixture was evaporated in vacuo, aqueous solution bicarbonate (5 ml.) was added and the mixture extracted with EtOAc (2×25 ml.) After drying (MgSO4) the solution was filtered and evaporated in vacuo to give a pale yellow solid. This was purified by medium pressure liquid chromatography on silica eluted with MeOH/CH2Cl2 (1:10 v/v) to give a solid. This was dissolved in EtOAc containing a trace of EtOH and excess of a solution of maleic acid in EtOAc was added. The resulting precipitate was collected by filtration and recrystallised from EtOH to give 4-[ 6-(2-[2,2,2-trifluoroethyl]guanidino)pyrazin-2-ylthio]butyramide maleate, m.p. 171°-172° (30% yield).

Workup

  1. stirringthe mixture stirred again for 30 minutes
  2. customto rise to room temperature
  3. customThe mixture was evaporated in vacuo, aqueous solution bicarbonate (5 ml.)
  4. additionwas added
  5. extractionthe mixture extracted with EtOAc (2×25 ml.)
  6. dry with materialAfter drying (MgSO4) the solution
  7. filtrationwas filtered
  8. customevaporated in vacuo
  9. customto give a pale yellow solid
  10. customThis was purified by medium pressure liquid chromatography on silica
  11. washeluted with MeOH/CH2Cl2 (1:10 v/v)
  12. customto give a solid
  13. filtrationThe resulting precipitate was collected by filtration
  14. customrecrystallised from EtOH

Sources & evidence

ORD record
ord-50115894523c4475a14cd4959132bee1
Source dataset
uspto-grants-1984_05
Patent number
US04447441

Reaction notes

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