1,3-Cyclohexanedione → HCID 178470346, compound

HRID 1696655Notes

Reaction equation

HRID 1696655 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].[Cl:12][C:13]1[CH:14]=[CH:15][C:16]2[N:20]=[C:19]([S:21][C:22]3[O:26][C:25]([CH:27]=O)=[CH:24][CH:23]=3)[NH:18][C:17]=2[CH:29]=1.[C:30]1(=O)[CH2:35][CH2:34][CH2:33][C:32](=[O:36])[CH2:31]1>C(O)C>[CH2:10]([O:9][C:7]([C:3]1[NH:4][CH:5]=[C:6]2[CH:27]([C:25]3[O:26][C:22]([S:21][C:19]4[NH:20][C:16]5[CH:15]=[CH:14][C:13]([Cl:12])=[CH:29][C:17]=5[N:18]=4)=[CH:23][CH:24]=3)[C:31]3[C:32](=[O:36])[CH2:33][CH2:34][CH2:35][C:30]=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 866238815-(6-chloro-1H-benzimidazol-2-ylsulfanyl)-furan-2-carbaldehyde

Product 1

HCID 178470346HCID 178470346, compoundYield 12.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 3-amino-2-ethoxycarbonyl-pyrrole (0.276 g 1.79 mmol), 5-(6-chloro-1H-benzimidazol-2-ylsulfanyl)-furan-2-carbaldehyde (0.5 g, 1.79 mmol) and 1,3-cyclohexanedione (0.201 g, 1.79 mmol) in 5 ml of ethanol is heated at reflux temperature for 2 hours. The reaction mixture is then concentrated under reduced pressure and 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 concentrated under reduced pressure and then purified using preparative LC/MS method B on a Xbridge C18 column (Waters, 30*100 mm) eluted with a 0 to 50% gradient of acetonitrile in aqueous 10 mM ammonium formate pH=9.0 at a 30 ml/min. flow rate in 12 min. The fraction containing the expected product are concentrated under reduced pressure. The residue is resuspended in 2 ml of acetonitrile, heated at reflux temperature and cold to room temperature. The insoluble material is collected by filtration, washed with diisopropyl ether (2×2 ml) and dried under vacuum to yield 115 mg of 9-[5-(5-chloro-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=12%. Analytical LC/MS (method B): m/z=509 (positive ion mode, [M+H]+, 1 Cl present), m/z=507 (negative ion mode, [M−H]−, 1 Cl present)

Workup

  1. temperatureis heated
  2. temperatureat reflux temperature for 2 hours
  3. concentrationThe reaction mixture is then concentrated under reduced pressure
  4. custompurified on a silica gel column (120 g)
  5. washeluted with a mixture of dichloromethane and methanol (99/1
  6. additionThe fractions containing the expected products
  7. concentrationare concentrated under reduced pressure
  8. custompurified
  9. washeluted with a 0 to 50% gradient of acetonitrile in aqueous 10 mM ammonium formate pH=9.0 at a 30 ml/min. flow rate in 12 min
  10. additionThe fraction containing the expected product
  11. concentrationare concentrated under reduced pressure
  12. temperatureheated
  13. temperatureat reflux temperature
  14. customcold to room temperature
  15. filtrationThe insoluble material is collected by filtration
  16. washwashed with diisopropyl ether (2×2 ml)
  17. customdried under vacuum

Sources & evidence

ORD record
ord-27b53940c49c4952b16eb2b3703aa4aa
Source dataset
uspto-grants-2012_04
Patent number
US08163768B2

Reaction notes

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