Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1) → HCID 66599202, compound

HRID 1889117Notes

Reaction equation

HRID 1889117 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[C:6]([Cl: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+](C)C.[CH3:28][C:29]1[C:30]([C:34]([NH:36][NH2:37])=O)=[N:31][S:32][CH:33]=1>ClCCl>[Cl:1][C:2]1[C:7]([F:8])=[C:6]([Cl:9])[CH:5]=[CH:4][C:3]=1[C:10]([N:12]1[CH2:17][CH2:16][N:15]2[C:34]([C:30]3[C:29]([CH3:28])=[CH:33][S:32][N:31]=3)=[N:36][N:37]=[C:14]2[CH2:13]1)=[O:11]

Participants

5

Reactant 3

HCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 66599027HCID 66599027, compoundHCID 665993614-[(2,4-Dichloro-3-fluorophenyl)carbonyl]-2-piperazinone

Product 1

HCID 66599202HCID 66599202, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-[(2,4-Dichloro-3-fluorophenyl)carbonyl]-2-piperazinone (I37) (90 mg, 0.309 mmol) was suspended in dichloromethane (DCM) (1.5 mL) before treating with trimethyloxonium tetrafluoroborate (57.8 mg, 0.371 mmol) and stirring for 16 hours at RT under argon before adding 4-methyl-3-isothiazolecarbohydrazide (I129)(58.3 mg, 0.371 mmol) and stirring for 4 hours. Adding 1-butanol (1.500 mL) then removing the DCM by evaporation before heating at 110° C. for 3 hours. As LCMS indicated that some start material remained, the reaction mixture was left heating for a further 17 hours. The reaction was worked up by diluting with DCM (30 ml) and washing with saturated sodium bicarbonate solution (30 ml). The aqueous layer was extracted with DCM (2×20 ml), the combined extracts were washed with brine (20 ml), dried (MgSO4), filtered and evaporated to afford a brown gum, 120 mg. The gum was purified by MDAP, the desired fraction isolated and the solvent evaporated to afford a white solid. The solid dried over the weekend in the vac oven at 40° C. to afford an off white solid of desired product in 22 mg.

Workup

  1. stirringstirring for 4 hours
  2. customAdding 1-butanol (1.500 mL) then removing the DCM
  3. customby evaporation
  4. temperaturebefore heating at 110° C. for 3 hours
  5. waitthe reaction mixture was left
  6. temperatureheating for a further 17 hours
  7. additionby diluting with DCM (30 ml)
  8. washwashing with saturated sodium bicarbonate solution (30 ml)
  9. extractionThe aqueous layer was extracted with DCM (2×20 ml)
  10. washthe combined extracts were washed with brine (20 ml)
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. customevaporated
  14. customto afford a brown gum, 120 mg
  15. customThe gum was purified by MDAP
  16. customthe desired fraction isolated
  17. customthe solvent evaporated
  18. customto afford a white solid
  19. customThe solid dried over the weekend in the vac oven at 40° C.

Sources & evidence

ORD record
ord-2406863d9dfa48f1b3a4d423c69b0003
Source dataset
uspto-grants-2013_08
Patent number
US08501946B2

Reaction notes

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