1,3-Cyclohexanedione → 8-Oxo-9-[5-(5-trifluoromethyl-1H-benzimidazol-2-ylsulfanyl)-furan-2-yl]-4,5,6,7,8,9-hexahydro-2H-pyrrolo[3,4-b]quinoline-3-carboxylic acid ethyl ester

HRID 1696659Notes

Reaction equation

HRID 1696659 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][C:13]([F:32])([F:31])[C:14]1[CH:15]=[CH:16][C:17]2[N:21]=[C:20]([S:22][C:23]3[O:27][C:26]([CH:28]=O)=[CH:25][CH:24]=3)[NH:19][C:18]=2[CH:30]=1.[C:33]1(=[O:40])[CH2:38][CH2:37][CH2:36][C:35](=O)[CH2:34]1>C(O)C>[CH2:10]([O:9][C:7]([C:3]1[NH:4][CH:5]=[C:6]2[CH:28]([C:26]3[O:27][C:23]([S:22][C:20]4[NH:21][C:17]5[CH:16]=[CH:15][C:14]([C:13]([F:32])([F:12])[F:31])=[CH:30][C:18]=5[N:19]=4)=[CH:24][CH:25]=3)[C:38]3[C:33](=[O:40])[CH2:34][CH2:35][CH2:36][C:37]=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 866238825-(6-trifluoromethyl-1H-benzimidazol-2-ylsulfanyl)-furan-2-carbaldehyde

Product 1

HCID 1784703458-Oxo-9-[5-(5-trifluoromethyl-1H-benzimidazol-2-ylsulfanyl)-furan-2-yl]-4,5,6,7,8,9-hexahydro-2H-pyrrolo[3,4-b]quinoline-3-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 3-amino-2-ethoxycarbonyl-pyrrole (0.355 g 2.31 mmol), 5-(6-trifluoromethyl-1H-benzimidazol-2-ylsulfanyl)-furan-2-carbaldehyde (0.72 g, 2.31 mmol) and 1,3-cyclohexanedione (0.259 g, 2.31 mmol) in 5 ml ethanol is heated at reflux temperature for 1 hour. The formed insoluble material is filtered off, the filtrate is concentrated under reduced pressure and purified on a silica gel column (120 g) eluted with a mixture of cyclohexane and ethylacetate (7/3, v/v). The fractions containing the expected product are concentrated under reduced pressure and purified via preparative LC/MS method B on a XBridge C18 column (Waters, 30*100 mm) eluted with a 0 to 50% in 12 min. gradient of acetonitrile in 10 mM aqueous ammonium formate pH=9.0 at a 30 ml/min. flow rate to deliver 56 mg of 8-oxo-9-[5-(5-trifluoromethyl-1H-benzimidazol-2-ylsulfanyl)-furan-2-yl]-4,5,6,7,8,9-hexahydro-2H-pyrrolo[3,4-b]quinoline-3-carboxylic acid ethyl ester. Yield=4%.

Workup

  1. temperatureis heated
  2. temperatureat reflux temperature for 1 hour
  3. filtrationThe formed insoluble material is filtered off
  4. concentrationthe filtrate is concentrated under reduced pressure
  5. custompurified on a silica gel column (120 g)
  6. washeluted with a mixture of cyclohexane and ethylacetate (7/3
  7. additionThe fractions containing the expected product
  8. concentrationare concentrated under reduced pressure
  9. custompurified via preparative LC/MS method B on a XBridge C18 column (Waters, 30*100 mm)
  10. washeluted with a 0 to 50% in 12 min. gradient of acetonitrile in 10 mM aqueous ammonium formate pH=9.0 at a 30 ml/min. flow rate

Sources & evidence

ORD record
ord-4bd970a7c51e4b37ba1f31b9677d0c10
Source dataset
uspto-grants-2012_04
Patent number
US08163768B2

Reaction notes

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