1,3-Cyclohexanedione → HCID 59825704, compound

HRID 1696634Notes

Reaction equation

HRID 1696634 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]1[C:29]([F:30])=[CH:28][C:16]2[NH:17][C:18]([S:20][C:21]3[O:25][C:24]([CH:26]=O)=[CH:23][CH:22]=3)=[N:19][C:15]=2[CH:14]=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:26]([C:24]3[O:25][C:21]([S:20][C:18]4[NH:19][C:15]5[CH:14]=[C:13]([F:12])[C:29]([F:30])=[CH:28][C:16]=5[N:17]=4)=[CH:22][CH:23]=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 866238745-(5,6-difluoro-1H-benzimidazol-2-ylsulfanyl)-furan-2-carbaldehyde

Product 1

HCID 59825704HCID 59825704, compoundYield 18.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A suspension of 308.3 mg (2.0 mmol) of 3-amino-2-ethoxycarbonylpyrrole and 560.5 mg (2.0 mmol) of 5-(5,6-difluoro-1H-benzimidazol-2-ylsulfanyl)-furan-2-carbaldehyde (obtained from step 1) in 10 mL of ethanol under argon is stirred at room temperature for 1 hour. 1,3-Cyclohexanedione (224.3 mg, 2.0 mmol) is then added and the reaction mixture is heated at reflux temperature for 16 h. The mixture is then cooled in an ice bath and the precipitate is filtered. The filtrate is concentrated to dryness under reduced pressure and the residue is purified by chromatography on a prepacked 90 g 15-40 μm silica gel cartridge (eluting solvent: ethyl acetate/cyclohexane 50/50 v/v; rate: 40 mL/min). The fractions containing the desired product are combined and concentrated to dryness under reduced pressure. The residue is recrystallized from ethyl acetate/n-heptane and then from ethyl acetate, filtered and dried under reduced pressure. 189 mg of 9-[5-(5,6-difluoro-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 an off-white crystalline powder. mp: 160-170° C. LCMS: m/z 511: [M+H]+ (base peak); m/z 509: [M−H]− (base peak). The filtrate is concentrated to dryness under reduced pressure and the residue is purified by chromatography on a prepacked 90 g 15-40 μm silica gel cartridge (eluting solvent: ethyl acetate; rate: 40 mL/min). The fractions containing the desired product are combined and concentrated to dryness under reduced pressure. 220 mg of additional 9-[5-(5,6-difluoro-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 an off-white powder. mp: 160-170° C. LCMS: m/z 511: [M+H]+ (base peak); m/z 509: [M−H]− (base peak).

Workup

  1. temperaturethe reaction mixture is heated
  2. temperatureat reflux temperature for 16 h
  3. temperatureThe mixture is then cooled in an ice bath
  4. filtrationthe precipitate is filtered
  5. concentrationThe filtrate is concentrated to dryness under reduced pressure
  6. customthe residue is purified by chromatography on a prepacked 90 g 15-40 μm silica gel cartridge (eluting solvent: ethyl acetate/cyclohexane 50/50 v/v; rate: 40 mL/min)
  7. additionThe fractions containing the desired product
  8. concentrationconcentrated to dryness under reduced pressure
  9. customThe residue is recrystallized from ethyl acetate/n-heptane
  10. filtrationfrom ethyl acetate, filtered
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-da8b47b1caba47d288c8084b42584c70
Source dataset
uspto-grants-2012_04
Patent number
US08163768B2

Reaction notes

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