Ammonia → 8-Bromo-5-carbamoylmethyl-5,6-dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-dione

HRID 52474Notes

Reaction equation

HRID 52474 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[CH2:15][CH:14]([CH2:16][C:17]([OH:19])=O)[N:6]3[C:7](=[O:13])[C:8](=[O:12])[NH:9][C:10]([CH:11]=1)=[C:5]23.C([N:22](CC)CC)C.ClC(OCC(C)C)=O.N.Cl>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[CH2:15][CH:14]([CH2:16][C:17](=[O:19])[NH2:22])[N:6]3[C:7](=[O:13])[C:8](=[O:12])[NH:9][C:10]([CH:11]=1)=[C:5]23

Participants

7

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 100191838-bromo-5-carboxymethyl-5,6-dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-dione

Product 1

HCID 199632258-Bromo-5-carbamoylmethyl-5,6-dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-dioneYield 14%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 8-bromo-5-carboxymethyl-5,6-dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-dione (100 mg, 0.308 mmol)in DMF (2 mL)in the presence of triethylamine (64 μL, 0.461 mmol) was added isobutyl chloroformate (44 μL, 0.338 mmol) at -20° C. After being stirred for 10 min, aqueous 28% ammonia (94 μL, 1.538 mmol) was added at -20° C. The stirring was continued for 30 min at room temperature and 0.1N hydrochloric acid (20 mL) was added. The precipitates formed were collected by filtration, washed with water, and again suspended in aqueous sodium bicarbonate. The suspension was adjusted to pH 7.0 by addition of 1N hydrochloric acid and extracted with 2:1 ethyl acetate/THF. The organic layer was washed with brine, dried over magnesium chloride, and concentrated. The residual solids were rinsed with dichloromethane to give 14 mg of the title compound (14%): mp>300° C.; 1H NMR (270 MHz, DMSO-d6) δ12.10 (bs, 1H), 7.66 (s, 1H), 7.29 (s, 1H), 7.17 (s, 2H), 5.04~5.10 (m, 1H), 2.80 (dm, 1H, J=18 Hz), 2.58 (dm, 1H, J=14 Hz), 2.41 (m, 1H, J=14 Hz), 1.85~2.00 (m, 1H).

Workup

  1. waitThe stirring was continued for 30 min at room temperature
  2. customThe precipitates formed
  3. filtrationwere collected by filtration
  4. washwashed with water
  5. additionThe suspension was adjusted to pH 7.0 by addition of 1N hydrochloric acid
  6. extractionextracted with 2:1 ethyl acetate/THF
  7. washThe organic layer was washed with brine
  8. dry with materialdried over magnesium chloride
  9. concentrationconcentrated
  10. washThe residual solids were rinsed with dichloromethane

Sources & evidence

ORD record
ord-0f8423dc8c2548a88a90d02bb32ef0bb
Source dataset
uspto-grants-1997_04
Patent number
US05616586

Reaction notes

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