Sodium Iodide → HCID 56599144, compound

HRID 1750124Notes

Reaction equation

HRID 1750124 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10](C=C[C:13](=[O:17])[NH:14]2)=[CH:9][CH:8]=1.[Na+].[I-].[Cl:20][C:21]1[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:22]=1[CH:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1.C([O-])([O-])=O.[K+].[K+].CC#[N:42]>>[Cl:20][C:21]1[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:22]=1[CH:28]1[CH2:33][CH2:32][N:31]([CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]2[CH:8]=[CH:9][C:10]3[NH:42][C:13](=[O:17])[NH:14][C:15]=3[CH:16]=2)[CH2:30][CH2:29]1

Participants

6

Reactant 5

HCID 5238Sodium IodideHCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 107563157-(4-BROMOBUTOXY)-QUINOLINE-2(1H)-ONEHCID 17895683HCID 17895683, compound

Product 1

HCID 56599144HCID 56599144, compoundYield 20%

Procedure

A mixture of intermediate 48 (200 mg, 0.7 mmol) and NaI (210 mg, 1.4 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 47 (167 mg, 0.63 mmol) and anhydrous K2CO3 (386 mg, 2.8 mmol) were added to the mixture. The resulting mixture was heated to reflux and stirred overnight. Precipitated crystals were filtered off and the filtrate was evaporated under reduced pressure. The residue was extracted with EtOAc. The combined EtOAc layers were washed with brine, dried over anhydrous Na2SO4, concentrated in vacuo and purified by flash chromatography on silica gel column (elution with DCM/MeOH=5:1) to give 5-(4-(4-(2,3-dichlorophenyl)piperidin-1-yl)butoxy)-1H-benzo[d]imidazol-2(3H)-one (compound 24) (61 mg, 20%). 1H NMR (300 MHz, CDCl3): δ 9.59 (brs, 1H), 9.29 (brs, 1H), 7.33-7.30 (m, 2H), 7.20-7.13 (m, 1H), 6.92 (d, J=8.7 Hz, 1H), 6.65-6.59 (m, 2H), 3.94-3.91 (m, 2H), 3.15-3.04 (m, 3H), 2.51-2.49 (m, 2H), 2.15 (t, J=11.1 Hz, 2H), 1.90-1.74 (m, 8H). HPLC: 99%, RT 2.332 min. MS (ESI) m/z 434.0 [M+H]+. mp: 180-182° C.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 30 min
  3. temperatureThe resulting mixture was heated
  4. temperatureto reflux
  5. customPrecipitated crystals
  6. filtrationwere filtered off
  7. customthe filtrate was evaporated under reduced pressure
  8. extractionThe residue was extracted with EtOAc
  9. washThe combined EtOAc layers were washed with brine
  10. dry with materialdried over anhydrous Na2SO4
  11. concentrationconcentrated in vacuo
  12. custompurified by flash chromatography on silica gel column (elution with DCM/MeOH=5:1)

Sources & evidence

ORD record
ord-c8af6531d12a44fd92345bdd5fc89342
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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