N-bromobutanimide → 3-Bromo-7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine

HRID 1893411Notes

Reaction equation

HRID 1893411 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:12]([N:14]1[CH2:19][CH2:18][N:17]2[CH:20]=[CH:21][N:22]=[C:16]2[CH2:15]1)=[O:13].C1C(=O)N([Br:30])C(=O)C1>CN(C)C=O>[Br:30][C:20]1[N:17]2[CH2:18][CH2:19][N:14]([C:12]([C:3]3[CH:4]=[CH:5][CH:6]=[C:7]([C:8]([F:9])([F:10])[F:11])[C:2]=3[Cl:1])=[O:13])[CH2:15][C:16]2=[N:22][CH:21]=1

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 497850107-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine

Product 1

HCID 497852023-Bromo-7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

7-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine (E1) (5.68 g, 17.23 mmol) was dissolved in N,N-dimethylformamide (DMF) (100 mL) and treated with NBS (3.22 g, 18.09 mmol). The solution was stirred at 25° C. for 16 h and the bulk of the DMF was removed in vacuo. The residue was partitioned between dichloromethane (500 ml) and saturated sodium bicarbonate solution (100 ml). The aqueous phase was extracted with dichloromethane (5×100 ml) during which filtration through celite was required to remove emulsions and precipitated succinimide. The combined organic extracts were washed with brine (100 ml), dried over anhydrous sodium sulfate and concentrated to a crude oil. The crude product was purified by flash chromatography (Isolera, 340 g, 0-100% methanol:dichloromethane (1:9)/dichloromethane) to afford an oil that was triturated with hexane to afford a solid of desired product in 5.90 g.

Workup

  1. customthe bulk of the DMF was removed in vacuo
  2. customThe residue was partitioned between dichloromethane (500 ml) and saturated sodium bicarbonate solution (100 ml)
  3. extractionThe aqueous phase was extracted with dichloromethane (5×100 ml) during which filtration through celite
  4. customto remove emulsions
  5. customprecipitated succinimide
  6. washThe combined organic extracts were washed with brine (100 ml)
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated to a crude oil
  9. customThe crude product was purified by flash chromatography (Isolera, 340 g, 0-100% methanol:dichloromethane (1:9)/dichloromethane)
  10. customto afford an oil that
  11. customwas triturated with hexane

Sources & evidence

ORD record
ord-c992e81de6b545b0a58863e895703f93
Source dataset
uspto-grants-2013_08
Patent number
US08513248B2

Reaction notes

Loading…