1,3-Cyclohexanedione → HCID 178470353, compound

HRID 1696652Notes

Reaction equation

HRID 1696652 reaction equation
[NH2:1][C:2]1[CH:6]=[CH:5][NH:4][C:3]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8].[F:12][CH:13]([F:32])[O:14][C:15]1[CH:16]=[CH:17][C:18]2[N:22]=[C:21]([S:23][C:24]3[O:28][C:27]([CH:29]=O)=[CH:26][CH:25]=3)[NH:20][C:19]=2[CH:31]=1.[C:33]1(=O)[CH2:38][CH2:37][CH2:36][C:35](=[O:39])[CH2:34]1>C(O)C>[CH2:10]([O:9][C:7]([C:3]1[NH:4][CH:5]=[C:6]2[CH:29]([C:27]3[O:28][C:24]([S:23][C:21]4[NH:22][C:18]5[CH:17]=[CH:16][C:15]([O:14][CH:13]([F:12])[F:32])=[CH:31][C:19]=5[N:20]=4)=[CH:25][CH:26]=3)[C:34]3[C:35](=[O:39])[CH2:36][CH2:37][CH2:38][C:33]=3[NH:1][C:2]=12)=[O:8])[CH3:11]

Participants

5

Reactant 3

HCID 104341,3-CyclohexanedioneHCID 2773439Ethyl 3-amino-1H-pyrrole-2-carboxylateHCID 86623880HCID 86623880, compound

Product 1

HCID 178470353HCID 178470353, compoundYield 23.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 3-amino-2-ethoxycarbonyl-pyrrole (0.248 g, 1.61 mmol), 5-(6-difluoromethoxy-1H-benzimidazol-2-ylsulfanyl)-furan-2-carbaldehyde (0.5 g, 1.61 mmol) and 1,3-cyclohexanedione (0.181 g 1.61 mmol) in 5 ml of ethanol is heated at reflux temperature for 2 hours. The reaction mixture is then concentrated under reduced pressure and dissolved in 5 ml of ethyl acetate. The organic phase is washed twice with 2 ml of water, dried over MgSO4 and concentrated under reduced pressure. The residue is purified on a silica gel column (120 g) eluted with a mixture of dichloromethane and methanol (99/1, v/v). The fractions containing the expected products are pooled and concentrated under reduced pressure. The residue is resuspended in 20 ml of acetonitrile, the mixture is heated at reflux temperature for 15 minutes and then let to cool to room temperature. The insoluble material is collected by filtration and dried under vacuum for 1 hour at 30° C. to yield 203 mg of 9-[5-(5-difluoromethoxy-1H-benzimidazol-2-ylsulfanyl)-furan-2-yl]-8-oxo-4,5,6,7,8,9-hexahydro-2H-pyrrolo[3,4-b]quinoline-3-carboxylic acid ethyl ester as a white powder. Yield=23%. Analytical LC/MS method B: m/z=541 (positive ion mode [M+H]+), m/z=539 (negative ion mode [M−H]−)

Workup

  1. temperatureis heated
  2. temperatureat reflux temperature for 2 hours
  3. concentrationThe reaction mixture is then concentrated under reduced pressure
  4. dissolutiondissolved in 5 ml of ethyl acetate
  5. washThe organic phase is washed twice with 2 ml of water
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is purified on a silica gel column (120 g)
  9. washeluted with a mixture of dichloromethane and methanol (99/1
  10. additionThe fractions containing the expected products
  11. concentrationconcentrated under reduced pressure
  12. temperaturethe mixture is heated
  13. temperatureat reflux temperature for 15 minutes
  14. filtrationThe insoluble material is collected by filtration
  15. customdried under vacuum for 1 hour at 30° C.

Sources & evidence

ORD record
ord-86b45d32f8dc4ee89e5cd6533abf0a79
Source dataset
uspto-grants-2012_04
Patent number
US08163768B2

Reaction notes

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