1,3-Cyclohexanedione → HCID 178470352, compound

HRID 1696629Notes

Reaction equation

HRID 1696629 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].[CH3:12][O:13][C:14]1[CH:30]=[CH:29][C:17]2[NH:18][C:19]([S:21][C:22]3[O:26][C:25]([CH:27]=O)=[CH:24][CH:23]=3)=[N:20][C:16]=2[CH:15]=1.[C:31]1(=O)[CH2:36][CH2:35][CH2:34][C:33](=[O:37])[CH2:32]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:18][C:17]5[CH:29]=[CH:30][C:14]([O:13][CH3:12])=[CH:15][C:16]=5[N:20]=4)=[CH:23][CH:24]=3)[C:32]3[C:33](=[O:37])[CH2:34][CH2:35][CH2:36][C:31]=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 178488111HCID 178488111, compound

Product 1

HCID 178470352HCID 178470352, compoundYield 21.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A suspension of 462.5 mg (3.0 mmol) of 3-amino-2-ethoxycarbonylpyrrole and 822.9 mg (3.0 mmol) of 5-(5-methoxy-1H-benzimidazol-2-ylsulfanyl)-furan-2-carbaldehyde (obtained from step 1) in 15 mL of ethanol under argon is stirred at room temperature for 1 hour. 1,3-Cyclohexanedione (336.4 mg, 3.0 mmol) is then added and the reaction mixture is heated at reflux temperature for 16 h. The mixture is then cooled to 0° C., filtered and the precipitate is washed with diisopropyl ether. The solid is then purified by chromatography on a prepacked 90 g 15-40 μm silica gel cartridge (eluting solvent: ethyl acetate/methanol/trifluoroacetic acid 98/1/1 v/v/v; rate: 40 mL/min). The fractions containing the desired product are combined and concentrated to dryness under reduced pressure. The residue is purified by chromatography on a prepacked 90 g 15-40 μm silica gel cartridge (eluting solvent: ethyl acetate/cyclohexane from 50/50 to 75/25 v/v; rate: 40 mL/min). The fractions containing the desired product are combined and concentrated to dryness under reduced pressure. 330 mg of 9-[5-(5-methoxy-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 are obtained as a yellow powder. mp: 140° C. LCMS: m/z 505: [M+H]+ (base peak); m/z 503: [M−H]− (base peak).

Workup

  1. temperaturethe reaction mixture is heated
  2. temperatureat reflux temperature for 16 h
  3. temperatureThe mixture is then cooled to 0° C.
  4. filtrationfiltered
  5. washthe precipitate is washed with diisopropyl ether
  6. customThe solid is then purified by chromatography on a prepacked 90 g 15-40 μm silica gel cartridge (eluting solvent: ethyl acetate/methanol/trifluoroacetic acid 98/1/1 v/v/v; rate: 40 mL/min)
  7. additionThe fractions containing the desired product
  8. concentrationconcentrated to dryness under reduced pressure
  9. customThe residue is purified by chromatography on a prepacked 90 g 15-40 μm silica gel cartridge (eluting solvent: ethyl acetate/cyclohexane from 50/50 to 75/25 v/v; rate: 40 mL/min)
  10. additionThe fractions containing the desired product
  11. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-97e11eca872649a2b06c327d555062fe
Source dataset
uspto-grants-2012_04
Patent number
US08163768B2

Reaction notes

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