4-Methyl-1,2,3-thiadiazole-5-carbohydrazide → 7-[(2,4-Dichloro-3-fluorophenyl)carbonyl]-3-(4-methyl-1,2,3-thiadiazol-5-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

HRID 1889100Notes

Reaction equation

HRID 1889100 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].[CH3:31][C:32]1[N:33]=[N:34][S:35][C:36]=1[C:37]([NH:39][NH2:40])=O>ClCCl>[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:37]([C:36]3[S:35][N:34]=[N:33][C:32]=3[CH3:31])=[N:39][N:40]=[C:26]2[CH2:25]1)=[O:23]

Participants

5

Reactant 3

HCID 14197524-Methyl-1,2,3-thiadiazole-5-carbohydrazideHCID 2723982Triethyloxonium tetrafluoroborateHCID 665993614-[(2,4-Dichloro-3-fluorophenyl)carbonyl]-2-piperazinone

Product 1

HCID 665991297-[(2,4-Dichloro-3-fluorophenyl)carbonyl]-3-(4-methyl-1,2,3-thiadiazol-5-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethyloxonium tetrafluoroborate (330 mg, 1.738 mmol) was added to a suspension of 4-[(2,4-dichloro-3-fluorophenyl)carbonyl]-2-piperazinone (I37) (460 mg, 1.580 mmol) in dry Dichloromethane (DCM) (3.9 ml). The reaction mixture was stirred at room temperature 45 mins—mixture became clear. 4-Methyl-1,2,3-thiadiazole-5-carbohydrazide (300 mg, 1.896 mmol, commercially available) was added and the resulting reaction mixture was stirred at room temperature 2 h 10 min. The solvent was evaporated under reduced pressure. The residue was dissolved in 1-butanol (3.90 ml) and the reaction mixture was stirred at reflux for 17 h. The reaction mixture was diluted in ethyl acetate (150 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 ether (5×2 mL) and then dried under vacuum at 50° C. to afford the desired product in 117.4 mg as a cream powder.

Workup

  1. customthe resulting reaction mixture
  2. stirringwas stirred at room temperature 2 h 10 min
  3. customThe solvent was evaporated under reduced pressure
  4. dissolutionThe residue was dissolved in 1-butanol (3.90 ml)
  5. stirringthe reaction mixture was stirred
  6. temperatureat reflux for 17 h
  7. additionThe reaction mixture was diluted in ethyl acetate (150 mL)
  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 ether (5×2 mL)
  13. customdried under vacuum at 50° C.

Sources & evidence

ORD record
ord-63e870b672844b50a0db2ae380c86d73
Source dataset
uspto-grants-2013_08
Patent number
US08501946B2

Reaction notes

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