Triethyloxonium tetrafluoroborate → 7-[(2,3-Dichloro-4-fluorophenyl)carbonyl]-3-(3-pyridazinyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

HRID 1889090Notes

Reaction equation

HRID 1889090 reaction equation
[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][CH:34]=[C:33]([C:37]([NH:39][NH2:40])=O)[N:32]=1>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:33]3[N:32]=[N:31][CH:36]=[CH:35][CH:34]=3)=[N:39][N:40]=[C:14]2[CH2:13]1)=[O:11]

Participants

5

Reactant 3

HCID 2723982Triethyloxonium tetrafluoroborateHCID 44119198Pyridazine-3-carbohydrazideHCID 665993354-[(2,3-Dichloro-4-fluorophenyl)carbonyl]-2-piperazinone

Product 1

HCID 665992417-[(2,3-Dichloro-4-fluorophenyl)carbonyl]-3-(3-pyridazinyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

4-[(2,3-Dichloro-4-fluorophenyl)carbonyl]-2-piperazinone (I34) (0.23 g, 0.790 mmol) was dissolved in Dichloromethane (DCM) (1.975 ml) and triethyloxonium tetrafluoroborate (0.180 g, 0.948 mmol) was added. The solution was left to stir under an argon atmosphere for 40 minutes. A clear solution was formed. 3-pyridazinecarbohydrazide (I23) (0.131 g, 0.948 mmol) was added and the solution was stirred under an argon atmosphere for a further 40 minutes. The solvent was removed under reduced pressure and then 1-butanol (1.975 ml) was added and the solution was left to reflux under an argon atmosphere at 120° C. for 3 hours. The reaction was followed by LCMS. The solvent was removed under reduced pressure. The crude material was purified by flash chromatography (Biotage SP4, 50 g cartridge) with a gradient of MeOH 0-10% in DCM. The solvent was removed under reduced pressure and the isolated material was purified further using MDAP. The columns were combined and the solvent removed under reduced pressure. The material was triturated with ether to afford the desired material in 27 mg.

Workup

  1. waitThe solution was left
  2. customA clear solution was formed
  3. stirringthe solution was stirred under an argon atmosphere for a further 40 minutes
  4. customThe solvent was removed under reduced pressure
  5. addition1-butanol (1.975 ml) was added
  6. waitthe solution was left
  7. customThe solvent was removed under reduced pressure
  8. customThe crude material was purified by flash chromatography (Biotage SP4, 50 g cartridge) with a gradient of MeOH 0-10% in DCM
  9. customThe solvent was removed under reduced pressure
  10. customthe isolated material was purified further using MDAP
  11. customthe solvent removed under reduced pressure
  12. customThe material was triturated with ether

Sources & evidence

ORD record
ord-0d1a9e6ee20942f39aab6447d7a2ec33
Source dataset
uspto-grants-2013_08
Patent number
US08501946B2

Reaction notes

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