Hydrochloric Acid → HCID 25110655, compound

HRID 1894738Notes

Reaction equation

HRID 1894738 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C:11]1[C:12](=[O:29])[NH:13][C:14](=[O:28])[C:15]=1[C:16]1[CH:17]=[C:18]2[C:23]3=[C:24]([CH:26]=[CH:27][N:22]3[CH2:21][CH2:20][CH2:19]2)[CH:25]=1.[Mg].Cl>CO.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C@H:11]1[C@H:15]([C:16]2[CH:17]=[C:18]3[C:23]4=[C:24]([CH:26]=[CH:27][N:22]4[CH2:21][CH2:20][CH2:19]3)[CH:25]=2)[C:14](=[O:28])[NH:13][C:12]1=[O:29]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 5462224MagnesiumHCID 59409005HCID 59409005, compound

Product 1

HCID 25110655HCID 25110655, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of 3-(5-bromo-1H-indol-3-yl)-4-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-8-yl)-pyrrole-2,5-dione (250 mg, 0.559 mmol) in methanol (35 ml) was added magnesium turnings (354 mg, 14.57 mmol) portionwise over 20 minutes and the mixture was heated to reflux for 6 hours. The mixture was cooled and diluted with water (50 ml) and acidified with 2M aqueous hydrochloric acid. The mixture was extracted with dichloromethane (3×50 ml) and the combined organic extracts were dried over anhydrous sodium sulfate and evaporated to dryness. The residue was purified (Xterra C18, reverse phase column, eluted with acetonitrile-water system with 0.1% trifluoracetic acid as modifier) to provide (±)-trans-3-(5-bromo-1H-indol-3-yl)-4-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-8-yl)-pyrrolidine-2,5-dione as a brown solid (45 mg). M.p.=195-200° C.; 400 MHz 1H NMR (DMSO-d6) δ: 11.41 (s, 1H), 11.24 (s, 1H), 7.99 (d, J=2.0 Hz, 1H), 7.47 (d, J=2.0 Hz, 1H), 7.30 (m, 3H), 7.17 (dd, J=8.4 and 2.0 Hz, 1H), 6.83 (s, 1H), 4.53 (d, J=7.6 Hz, 1H), 4.38 (d, J=7.6 Hz, 1H), 4.13 (m, 2H), 2.90 (t, J=6.0 Hz, 2H), 2.11 (m, 2H); LCMS: 448 and 450 [M+H].

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 6 hours
  3. temperatureThe mixture was cooled
  4. extractionThe mixture was extracted with dichloromethane (3×50 ml)
  5. dry with materialthe combined organic extracts were dried over anhydrous sodium sulfate
  6. customevaporated to dryness
  7. customThe residue was purified
  8. wash(Xterra C18, reverse phase column, eluted with acetonitrile-water system with 0.1% trifluoracetic acid as modifier)

Sources & evidence

ORD record
ord-c14a731fa2fd456a8a08cab3070c1916
Source dataset
uspto-grants-2013_08
Patent number
US08513292B2

Reaction notes

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