Pyrazine-2-Carboxylic Acid Hydrazide → 7-[(2,3-Dichloro-4-fluorophenyl)carbonyl]-3-(2-pyrazinyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

HRID 1889082Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1889082
[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([F:9])[CH:5]=[CH:4][C:3]=1[C:10]([N:12]1[CH2:17][CH2:16][NH:15][C:14](=O)[CH2:13]1)=[O:11].F[B-](F)(F)F.C([O+](CC)CC)C.[N:31]1[CH:36]=[CH:35][N:34]=[CH:33][C:32]=1[C:37]([NH:39][NH2:40])=O>ClCCl>[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([F:9])[CH:5]=[CH:4][C:3]=1[C:10]([N:12]1[CH2:17][CH2:16][N:15]2[C:37]([C:32]3[CH:33]=[N:34][CH:35]=[CH:36][N:31]=3)=[N:39][N:40]=[C:14]2[CH2:13]1)=[O:11]

Komponenten

5

Edukt 3

HCID 258796Pyrazine-2-Carboxylic Acid HydrazideHCID 2723982Triethyloxonium tetrafluoroborateHCID 665993354-[(2,3-Dichloro-4-fluorophenyl)carbonyl]-2-piperazinone

Produkt 1

HCID 665993467-[(2,3-Dichloro-4-fluorophenyl)carbonyl]-3-(2-pyrazinyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

4-[(2,3-dichloro-4-fluorophenyl)carbonyl]-2-piperazinone (I34) (0.210 g, 0.721 mmol) was dissolved in Dichloromethane (DCM) (3 mL), and to this was added triethyloxonium tetrafluoroborate (0.144 g, 0.757 mmol), the solution was stirred for 20 minutes before 2-pyrazinecarbohydrazide (commercially available from e.g. TimTec, J&W PharmLab or AKos Consulting, 0.120 g, 0.866 mmol) was added. The solution was then allowed to stir for an additional 30 minutes before the solvent was concentrated and n-butanol (3 mL) was added. The solution was then stirred, under argon and reflux, for 3 hours before being allowed to cool to room temperature. The solvent was then removed in vacuo and the remaining residue was purified by flash chromatography (Biotage SP4, 25M cartridge) with a gradient of 0-10% 2M NH3/MeOH in DCM. TLC confirmed product location and the solvent from the combined fractions was evaporated in vacuo. The remaining residue was then further purified by mass-directed automated HPLC, and the solvent evaporated in vacuo. The remaining residue was then triturated with ether and dried in a vacuum oven to yield the product in 0.112 g.

Aufarbeitung

  1. additionwas added
  2. concentrationwas concentrated
  3. additionn-butanol (3 mL) was added
  4. stirringThe solution was then stirred, under argon
  5. temperaturereflux, for 3 hours
  6. customThe solvent was then removed in vacuo
  7. customthe remaining residue was purified by flash chromatography (Biotage SP4, 25M cartridge) with a gradient of 0-10% 2M NH3/MeOH in DCM
  8. customthe solvent from the combined fractions was evaporated in vacuo
  9. customThe remaining residue was then further purified
  10. customthe solvent evaporated in vacuo
  11. customThe remaining residue was then triturated with ether
  12. customdried in a vacuum oven
  13. customto yield the product in 0.112 g

Quellen und Nachweise

ORD-Eintrag
ord-8414c91653c746f5a2efc3a83124e025
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08501946B2

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