1,3-Cyclohexanedione → HCID 59825760, compound

HRID 1696638Notes

Reaction equation

HRID 1696638 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].[N:12]1[C:20]2[CH:19]=[CH:18][N:17]=[CH:16][C:15]=2[NH:14][C:13]=1[S:21][C:22]1[O:26][C:25]([CH:27]=O)=[CH:24][CH:23]=1.[C:29]1(=O)[CH2:34][CH2:33][CH2:32][C:31](=[O:35])[CH2:30]1>C(O)CCC>[CH2:10]([O:9][C:7]([C:3]1[NH:4][CH:5]=[C:6]2[CH:27]([C:25]3[O:26][C:22]([S:21][C:13]4[NH:14][C:15]5[CH:16]=[N:17][CH:18]=[CH:19][C:20]=5[N:12]=4)=[CH:23][CH:24]=3)[C:30]3[C:31](=[O:35])[CH2:32][CH2:33][CH2:34][C:29]=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 86623875HCID 86623875, compound

Product 1

HCID 59825760HCID 59825760, compoundYield 37.4%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A suspension of 154.2 mg (1.0 mmol) of 3-amino-2-ethoxycarbonylpyrrole and 245.3 mg (1.0 mmol) of 5-(3H-imidazo[4,5-c]pyridin-2-ylsulfanyl)-furan-2-carbaldehyde (obtained from step 1) in 10 mL of n-butanol under argon is stirred at room temperature for 15 min. 1,3-Cyclohexanedione (112.1 mg, 1.0 mmol) is then added and the reaction mixture is heated at reflux temperature for 2 h. The mixture is then cooled to room temperature and concentrated under reduced pressure. The residue is triturated in ethanol, filtered and washed with diethyl ether. The solid is purified by chromatography on a prepacked 70 g 15-40 μm silica gel cartridge (eluting solvent: dichloromethane/methanol from 100/0 to 80/20 v/v; rate: 40 mL/min). The fractions containing the desired product are combined and concentrated to dryness under reduced pressure. 178 mg of 9-[5-(3H-imidazo[4,5-c]pyridin-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 powder. LCMS: m/z 476: [M+H]+ (base peak). Anal. Calcd for C24H21N5O4S: C, 60.62; H, 4.45; N, 14.73; O, 13.46; S, 6.74. Found: C, 59.41; H, 4.47; N, 14.33; S, 6.41; H2O, 2.11%.

Workup

  1. temperaturethe reaction mixture is heated
  2. temperatureat reflux temperature for 2 h
  3. temperatureThe mixture is then cooled to room temperature
  4. concentrationconcentrated under reduced pressure
  5. customThe residue is triturated in ethanol
  6. filtrationfiltered
  7. washwashed with diethyl ether
  8. customThe solid is purified by chromatography on a prepacked 70 g 15-40 μm silica gel cartridge (eluting solvent: dichloromethane/methanol from 100/0 to 80/20 v/v; rate: 40 mL/min)
  9. additionThe fractions containing the desired product
  10. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-678e194cfecc45f3a73872029261e0de
Source dataset
uspto-grants-2012_04
Patent number
US08163768B2

Reaction notes

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