1,3-Cyclohexanedione → 8-oxo-9-[5-(5-trifluoromethoxy-1H-benzimidazol-2-ylsulfanyl)-furan-2-yl]-4,5,6,7,8,9-hexahydro-2H-pyrrolo[3,4-b]quinoline-3-carboxylic acid ethyl ester

HRID 1696681Notes

Reaction equation

HRID 1696681 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]([F:33])([F:32])[O:14][C:15]1[CH:31]=[CH:30][C:18]2[NH:19][C:20]([S:22][C:23]3[O:27][C:26]([CH:28]=O)=[CH:25][CH:24]=3)=[N:21][C:17]=2[CH:16]=1.[C:34]1(=O)[CH2:39][CH2:38][CH2:37][C:36](=[O:40])[CH2:35]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:20]4[NH:19][C:18]5[CH:30]=[CH:31][C:15]([O:14][C:13]([F:32])([F:33])[F:12])=[CH:16][C:17]=5[N:21]=4)=[CH:24][CH:25]=3)[C:35]3[C:36](=[O:40])[CH2:37][CH2:38][CH2:39][C:34]=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 178519733HCID 178519733, compound

Product 1

HCID 1784703548-oxo-9-[5-(5-trifluoromethoxy-1H-benzimidazol-2-ylsulfanyl)-furan-2-yl]-4,5,6,7,8,9-hexahydro-2H-pyrrolo[3,4-b]quinoline-3-carboxylic acid ethyl esterYield 36.5%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A mixture of 3-amino-2-ethoxycarbonyl-pyrrole (0.235 g, 1.52 mmol), 5-(5-trifluoromethoxy-1H-benzoimidazol-2-ylsulfanyl)-furan-2-carbaldehyde (0.50 g, 1.52 mmol) and 1,3-cyclohexanedione (0.171 g, 1.52 mmol) in 5 ml of 1-butanol is heated at reflux temperature for 4 hours. The reaction mixture is then concentrated under reduced pressure. The residue is then purified on a silica gel column (40 g) eluted successively with cyclohexane/ethyl acetate (7/3, v/v) and cyclohexane/ethyl acetate (1/1, v/v). The fractions containing the expected product are concentrated under reduced pressure. The obtained solid is washed with acetonitrile (100 ml), pentane (50 ml) and dried under vacuum to yield 310 mg of 8-oxo-9-[5-(5-trifluoromethoxy-1H-benzimidazol-2-ylsulfanyl)-furan-2-yl]-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 C): m/z=559 (positive ion mode [M+H]+), m/z=557 (negative ion mode [M−H]−).

Workup

  1. temperatureis heated
  2. temperatureat reflux temperature for 4 hours
  3. concentrationThe reaction mixture is then concentrated under reduced pressure
  4. customThe residue is then purified on a silica gel column (40 g)
  5. washeluted successively with cyclohexane/ethyl acetate (7/3
  6. additionThe fractions containing the expected product
  7. concentrationare concentrated under reduced pressure
  8. washThe obtained solid is washed with acetonitrile (100 ml), pentane (50 ml)
  9. customdried under vacuum

Sources & evidence

ORD record
ord-470a28f227c749c3af1855820bfaf671
Source dataset
uspto-grants-2012_04
Patent number
US08163768B2

Reaction notes

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