HCID 1382089, compound → HCID 66599246, compound

HRID 1889107Notes

Reaction equation

HRID 1889107 reaction equation
F[B-](F)(F)F.C([O+](CC)CC)C.[Cl:13][C:14]1[C:19]([F:20])=[C:18]([Cl:21])[CH:17]=[CH:16][C:15]=1[C:22]([N:24]1[CH2:29][CH2:28][NH:27][C:26](=O)[CH2:25]1)=[O:23].[S:31]1[N:35]=[CH:34][C:33]([C:36]([NH:38][NH2:39])=O)=[N:32]1>ClCCl.C(OCC)(=O)C>[Cl:13][C:14]1[C:19]([F:20])=[C:18]([Cl:21])[CH:17]=[CH:16][C:15]=1[C:22]([N:24]1[CH2:29][CH2:28][N:27]2[C:36]([C:33]3[CH:34]=[N:35][S:31][N:32]=3)=[N:38][N:39]=[C:26]2[CH2:25]1)=[O:23]

Participants

6

Reactant 3

HCID 1382089HCID 1382089, compoundHCID 2723982Triethyloxonium tetrafluoroborateHCID 665993614-[(2,4-Dichloro-3-fluorophenyl)carbonyl]-2-piperazinone

Product 1

HCID 66599246HCID 66599246, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Triethyloxonium tetrafluoroborate (144 mg, 0.756 mmol) was added under argon to a suspension of 4-[(2,4-dichloro-3-fluorophenyl)carbonyl]-2-piperazinone (I37) (200 mg, 0.687 mmol) in dry dichloromethane (DCM) (1.7 ml). The reaction mixture was stirred at room temperature for 1 h—everything dissolved. 1,2,5-thiadiazole-3-carbohydrazide (I119)(119 mg, 0.824 mmol) was added and the mixture was stirred at room temperature overnight. The solvent was evaporated under reduced pressure and 1-butanol (1.700 ml) was added to the residue. The resulting reaction mixture was stirred at reflux for 5 h. The reaction mixture was diluted with ethyl acetate (I25 mL) and washed with water (2×25 mL), sat. NaHCO3 (25 mL) and brine (2×25 mL). The resulting organic layer was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by MDAP (basic method). The resulting residue was triturated with Et2O and dried 3 days at 50° C. under vacuum. The resulting solid was triturated with n-hexane and dried at 50° C. under vacuum for 20 h. The resulting solid was triturated again with n-hexane and dried at 50° C. under vacuum overnight to afford the desired product in 37.5 mg as a white powder.

Workup

  1. dissolutiondissolved
  2. stirringthe mixture was stirred at room temperature overnight
  3. customThe solvent was evaporated under reduced pressure and 1-butanol (1.700 ml)
  4. additionwas added to the residue
  5. customThe resulting reaction mixture
  6. stirringwas stirred
  7. temperatureat reflux for 5 h
  8. washwashed with water (2×25 mL), sat. NaHCO3 (25 mL) and brine (2×25 mL)
  9. dry with materialThe resulting organic layer was dried over MgSO4
  10. concentrationconcentrated under reduced pressure
  11. customThe crude product was purified by MDAP (basic method)
  12. customThe resulting residue was triturated with Et2O
  13. customdried 3 days at 50° C. under vacuum
  14. customThe resulting solid was triturated with n-hexane
  15. customdried at 50° C. under vacuum for 20 h
  16. customThe resulting solid was triturated again with n-hexane
  17. customdried at 50° C. under vacuum overnight

Sources & evidence

ORD record
ord-c703eccff31d4f048bee5e6abc3f1dd4
Source dataset
uspto-grants-2013_08
Patent number
US08501946B2

Reaction notes

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