1,3-Cyclohexanedione → 9-[5-(5,6-dichloro-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

HRID 1696636Notes

Reaction equation

HRID 1696636 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[C:29]([Cl: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)CCC>[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]([Cl:12])[C:29]([Cl: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 714239795-[(5,6-Dichloro-1H-benzimidazol-2-yl)sulfanyl]furan-2-carbaldehyde

Product 1

HCID 598257199-[5-(5,6-dichloro-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 esterYield 52.9%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A suspension of 231.3 mg (1.5 mmol) of 3-amino-2-ethoxycarbonylpyrrole and 469.7 mg (1.5 mmol) of 5-(5,6-dichloro-1H-benzimidazol-2-ylsulfanyl)-furan-2-carbaldehyde (obtained from step 1) in 7.5 mL of n-butanol under argon is stirred at room temperature until complete dissolution. 1,3-Cyclohexanedione (168.2 mg, 1.5 mmol) is then added and the reaction mixture is heated at reflux temperature for 1.5 h. The mixture is then cooled to room temperature and concentrated under reduced pressure. The residue is purified by chromatography on a prepacked 90 g 15-40 μm silica gel cartridge (eluting solvent: dichloromethane/methanol 100/0 to 90/10 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 ethanol and the solid is filtered, washed with ethanol and dried under reduced pressure. 431 mg of 9-[5-(5,6-dichloro-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 beige crystalline powder. mp: 180° C. LCMS: m/z 543: [M+H]+ (base peak). EA.

Workup

  1. temperaturethe reaction mixture is heated
  2. temperatureat reflux temperature for 1.5 h
  3. temperatureThe mixture is then cooled to room temperature
  4. concentrationconcentrated under reduced pressure
  5. customThe residue is purified by chromatography on a prepacked 90 g 15-40 μm silica gel cartridge (eluting solvent: dichloromethane/methanol 100/0 to 90/10 v/v; rate: 40 mL/min)
  6. additionThe fractions containing the desired product
  7. concentrationconcentrated to dryness under reduced pressure
  8. customThe residue is recrystallized from ethanol
  9. filtrationthe solid is filtered
  10. washwashed with ethanol
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-d7a2ccf39d494ea5be3004f901093492
Source dataset
uspto-grants-2012_04
Patent number
US08163768B2

Reaction notes

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