Sodium Iodide → 5-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)propoxy)-1H-benzo[d]imidazol-2(3H)-one

HRID 1750139Notes

Reaction equation

HRID 1750139 reaction equation
Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:9]2[NH:10][C:11](=[O:13])[NH:12][C:8]=2[CH:7]=1.[Na+].[I-].Cl.[Cl:19][C:20]1[C:25]([Cl:26])=[CH:24][CH:23]=[CH:22][C:21]=1[N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.C([O-])([O-])=O.[K+].[K+]>CC#N>[Cl:19][C:20]1[C:25]([Cl:26])=[CH:24][CH:23]=[CH:22][C:21]=1[N:27]1[CH2:32][CH2:31][N:30]([CH2:2][CH2:3][CH2:4][O:5][C:6]2[CH:15]=[CH:14][C:9]3[NH:10][C:11](=[O:13])[NH:12][C:8]=3[CH:7]=2)[CH2:29][CH2:28]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 116303721-(2,3-Dichlorophenyl)piperazine hydrochlorideHCID 666336885-(3-bromopropoxy)-1H-benzo[d]imidazol-2(3H)-one

Product 1

HCID 565970945-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)propoxy)-1H-benzo[d]imidazol-2(3H)-oneYield 27.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of intermediate 39 (126 mg, 0.47 mmol) and NaI (140 mg, 0.93 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 41 (188 mg, 0.71 mmol) and anhydrous K2CO3 (259 mg, 1.88 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=15:1) to give 5-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)propoxy)-1H-benzo[d]imidazol-2(3H)-one (compound 34) (54 mg, 27%). 1H NMR (300 MHz, DMSO): δ 10.60 (s, 1H), 10.36 (s, 1H), 7.32 (d, J=5.1 Hz, 2H), 7.16-7.18 (m, 1H), 6.80 (d, J=9.6 Hz, 1H), 6.51-6.53 (d, J=6.6 Hz, 2H), 3.99-3.95 (m, 2H), 2.81-3.26 (s, 5H), 2.80-2.60 (m, 5H), 1.80-2.01 (m, 2H). HPLC: 99%, RT 2.228 min. MS (ESI) m/z 421.1 [M+H]+.

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=15:1)

Sources & evidence

ORD record
ord-8051285f56ee4a39836fe5a5ee30e7fb
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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