Thionyl Chloride → 3,4-Dihydropyrazino[1,2-a]benzimidazol-1(2H)-one

HRID 1918893Notes

Reaction equation

HRID 1918893 reaction equation
O[CH2:2][CH2:3][NH:4][C:5]([C:7]1[NH:11][C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[N:8]=1)=[O:6].S(Cl)(Cl)=O>CN(C=O)C>[C:5]1(=[O:6])[C:7]2=[N:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[N:8]2[CH2:2][CH2:3][NH:4]1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 24974388HCID 24974388, compound

Product 1

HCID 249743893,4-Dihydropyrazino[1,2-a]benzimidazol-1(2H)-oneYield 52.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was purged with nitrogen and charged with 152a (1.41 g, 6.84 mmol) and DMF (10 mL), and the reaction mixture was cooled to 0° C. A solution of thionyl chloride (896 mg, 7.53 mmol) in DMF (5 mL) was added dropwise. The reaction was heated at 150° C. for 2 h. After this time, the solvent was removed under reduced pressure. The resulting residue was partitioned between water (20 mL) and methylene chloride (20 mL). The layers were separated, and the aqueous phase was extracted with methylene chloride (2×20 mL). The organic extracts were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography to afford a 52% yield (672 mg) of 152b as a brown solid: mp>250° C.; 1H NMR (500 MHz, DMSO-d6) d 8.53 (s, 1H), 7.76 (d, 1H, J=9.0 Hz), 7.66 (d, 1H, J=9.0 Hz), 7.40 (t, 1H, J=9.0 Hz), 7.31 (t, 1H, J=9.0 Hz), 4.41 (t, 2H, J=6.0 Hz), 3.71 (m, 2H); MS (APCI+) m/z 188.4 (M+H).

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. customwas purged with nitrogen
  4. temperatureThe reaction was heated at 150° C. for 2 h
  5. customAfter this time, the solvent was removed under reduced pressure
  6. customThe resulting residue was partitioned between water (20 mL) and methylene chloride (20 mL)
  7. customThe layers were separated
  8. extractionthe aqueous phase was extracted with methylene chloride (2×20 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe resulting residue was purified by flash chromatography

Sources & evidence

ORD record
ord-0ee4006d2d7d48e0bbd5163da3facc0d
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

Loading…