Sodium Hydroxide → HCID 59825635, compound

HRID 1696650Notes

Reaction equation

HRID 1696650 reaction equation
C([O:3][C:4]([C:6]1[NH:7][CH:8]=[C:9]2[CH:18]([C:19]3[O:20][C:21]([S:24][C:25]4[NH:29][C:28]5[CH:30]=[CH:31][CH:32]=[CH:33][C:27]=5[N:26]=4)=[CH:22][CH:23]=3)[C:17]3[C:16](=[O:34])[CH2:15][C:14]([CH3:36])([CH3:35])[CH2:13][C:12]=3[NH:11][C:10]=12)=[O:5])C.[OH-].[Na+]>C(O)C.O>[NH:26]1[C:27]2[CH:33]=[CH:32][CH:31]=[CH:30][C:28]=2[N:29]=[C:25]1[S:24][C:21]1[O:20][C:19]([CH:18]2[C:17]3[C:16](=[O:34])[CH2:15][C:14]([CH3:36])([CH3:35])[CH2:13][C:12]=3[NH:11][C:10]3=[C:6]([C:4]([OH:5])=[O:3])[NH:7][CH:8]=[C:9]23)=[CH:23][CH:22]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 12000661HCID 12000661, compound

Product 1

HCID 59825635HCID 59825635, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
40 °C

Procedure

To a solution of 330 mg (0.657 mmol) of 9-[5-(1H-benzimidazol-2-ylsulfanyl)-furan-2-yl]-6,6-dimethyl-8-oxo-4,5,6,7,8,9-hexahydro-2H-pyrrolo[3,4-b]quinoline-3-carboxylic acid ethyl ester in 10 ml ethanol and 1 ml water was added 263 mg of sodium hydroxide in a round bottom flask. The reaction mixture was heated at 40° C. with stirring for 8 hours, and at 30° C. overnight. Water was added to the reaction mixture and it was extracted twice with ethyl acetate. The organic layers were washed with water and brine and dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting oily residue was dissolved in 1 ml methanol and 14 ml of dichloromethane and purified by chromatography on a prepacked 75 g 15-40 μm silica gel cartridge (eluting solvent: dichloromethane/methanol from 98/2 to 92/8 v/v in 50 min; rate: 40 mL/min). The fractions containing the desired product were combined and concentrated to dryness under reduced pressure giving 106 mg of 9-[5-(1H-benzimidazol-2-ylsulfanyl)-furan-2-yl]-6,6-dimethyl-8-oxo-4,5,6,7,8,9-hexahydro-2H-pyrrolo[3,4-b]quinoline-3-carboxylic acid (34% yield). Analytical LC/MS method B: [M+H]+=475.5; retention time: 3.01 min; 95% UV purity. 300 MHz 1H NMR (DMSO-d6) δ (ppm): 0.91 (s, 3H); 0.98 (s, 3H); 2.05 (d, J=17.0 Hz, 1H); 2.16 (d, J=17.0 Hz, 1H); 2.50 (d partially masked, J=17.0 Hz, 1H); 2.61 (d, J=17.0 Hz, 1H); 5.14 (s, 1H); 5.97 (d, J=3.5 Hz, 1H); 6.73 (d, J=3.0 Hz, 1H); 6.83 (d, J=3.5 Hz, 1H); de 7.10 à 7.20 (m, 2H); 7.40 (d large, J=8.0 Hz, 1H); 7.52 (d large, J=8.0 Hz, 1H); 8.32 (s large, 1H); 11.3 (s large, 1H); 12.25 (m wide, 1H); 12.3 (s large, 1H).

Workup

  1. customat 30° C.
  2. customovernight
  3. extractionwas extracted twice with ethyl acetate
  4. washThe organic layers were washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe resulting oily residue was dissolved in 1 ml methanol
  9. custom14 ml of dichloromethane and purified by chromatography on a prepacked 75 g 15-40 μm silica gel cartridge (eluting solvent: dichloromethane/methanol from 98/2 to 92/8 v/v in 50 min; rate: 40 mL/min)
  10. additionThe fractions containing the desired product
  11. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-e20d0c62bb6e404a918f7646b36430ef
Source dataset
uspto-grants-2012_04
Patent number
US08163768B2

Reaction notes

Loading…