1,3-Cyclohexanedione → HCID 59825774, compound

HRID 1696670Notes

Reaction equation

HRID 1696670 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:21]2[N:20]=[C:19]([S:22][C:23]3[O:27][C:26]([CH:28]=O)=[CH:25][CH:24]=3)[NH:18][C:17]=2[CH:16]=[C:15]([F:30])[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:28]([C:26]3[O:27][C:23]([S:22][C:19]4[NH:18][C:17]5[CH:16]=[C:15]([F:30])[CH:14]=[C:13]([F:12])[C:21]=5[N:20]=4)=[CH:24][CH:25]=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 86623886HCID 86623886, compound

Product 1

HCID 59825774HCID 59825774, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A mixture of 3-amino-2-ethoxycarbonyl-pyrrole (3.19 g, 20.7 mmol), 5-(4,6-difluoro-1H-benzimidazol-2-ylsulfanyl)-furan-2-carbaldehyde (5.80 g, 20.7 mmol) and 1,3-cyclohexanedione (2.32 g, 20.7 mmol) in 80 ml of 1-butanol is heated at reflux temperature for 3 hours. The reaction mixture is then concentrated under reduced pressure and the residue is purified on a silica gel column (150 g) eluted successively with cyclohexane/ethyl acetate (9/1, v/v) and cyclohexane/ethyl acetate (7/3, v/v). The fractions containing the expected product are concentrated under reduced pressure. The residue is resuspended in 100 ml of acetonitrile and heated at reflux temperature for 30 minutes. The mixture is allowed to cool to room temperature and the insoluble material is collected by filtration. The solid is washed with acetonitrile (400 ml), diisopropyl ether (100 ml) and pentane (100 ml) and dried under vacuum to yield 3.8 g of 9-[5-(4,6-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 as a white powder. Yield=36%. Analytical LC/MS method B: m/z=509 (negative ion mode [M−H]−), m/z=511 (positive ion mode [M+H]+).

Workup

  1. temperatureis heated
  2. temperatureat reflux temperature for 3 hours
  3. concentrationThe reaction mixture is then concentrated under reduced pressure
  4. customthe residue is purified on a silica gel column (150 g)
  5. washeluted successively with cyclohexane/ethyl acetate (9/1
  6. additionThe fractions containing the expected product
  7. concentrationare concentrated under reduced pressure
  8. temperatureheated
  9. temperatureat reflux temperature for 30 minutes
  10. filtrationthe insoluble material is collected by filtration
  11. washThe solid is washed with acetonitrile (400 ml), diisopropyl ether (100 ml) and pentane (100 ml)
  12. customdried under vacuum

Sources & evidence

ORD record
ord-12dd459371f146a2b5539ce0be5340a3
Source dataset
uspto-grants-2012_04
Patent number
US08163768B2

Reaction notes

Loading…