1,3-Cyclohexanedione → HCID 178470347, compound

HRID 1696664Notes

Reaction equation

HRID 1696664 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:29]=[C:28]([CH3:30])[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:17][C:16]5[C:28]([CH3:30])=[CH:29][C:13]([Cl:12])=[CH:14][C:15]=5[N:19]=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 178426085HCID 178426085, compound

Product 1

HCID 178470347HCID 178470347, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A mixture of 3-amino-2-ethoxycarbonyl-pyrrole (0.158 g, 1.02 mmol), 5-(5-chloro-7-methyl-1H-benzimidazol-2-ylsulfanyl)-furan-2-carbaldehyde (0.30 g, 1.02 mmol) and 1,3-cyclohexanedione (0.115 g, 1.02 mmol) in 5 ml of 1-butanol is heated at reflux temperature for 4 h. The reaction mixture is then concentrated under reduced pressure and the residue is purified on a silica gel column (34 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 the residue is triturated in diisopropylether and pentane. The obtained solid is then resuspended in 5 ml acetonitrile, heated at reflux temperature for 30 minutes and let to cool to room temperature. The insoluble material is collected by filtration and dried under vacuum to deliver 100 mg of 9-[5-(5-chloro-7-methyl-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. Yield=20%. Analytical LC/MS (method B): m/z=523 (positive ion mode [M+H]+, 1 Cl present), m/z=521 (negative ion mode [M−H]−, 1 Cl present).

Workup

  1. temperatureis heated
  2. temperatureat reflux temperature for 4 h
  3. concentrationThe reaction mixture is then concentrated under reduced pressure
  4. customthe residue is purified on a silica gel column (34 g)
  5. washeluted with a mixture of cyclohexane and ethylacetate (7/3
  6. additionThe fractions containing the expected product
  7. concentrationare concentrated under reduced pressure
  8. customthe residue is triturated in diisopropylether
  9. temperatureheated
  10. temperatureat reflux temperature for 30 minutes
  11. filtrationThe insoluble material is collected by filtration
  12. customdried under vacuum

Sources & evidence

ORD record
ord-bfe2500cd2a64edebfe8f53b553184ac
Source dataset
uspto-grants-2012_04
Patent number
US08163768B2

Reaction notes

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