Sodium Iodide → 7-((4-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)cyclohexyl)methoxy)-3,4-dihydroquinolin-2(1H)-one

HRID 1750127Notes

Reaction equation

HRID 1750127 reaction equation
Br[CH2:2][CH:3]1[CH2:8][CH2:7][CH:6]([CH2:9][O:10][C:11]2[CH:20]=[C:19]3[C:14]([CH2:15][CH2:16][C:17](=[O:21])[NH:18]3)=[CH:13][CH:12]=2)[CH2:5][CH2:4]1.[Na+].[I-].Cl.[Cl:25][C:26]1[C:31]([Cl:32])=[CH:30][CH:29]=[CH:28][C:27]=1[N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.C([O-])([O-])=O.[K+].[K+]>CC#N>[Cl:25][C:26]1[C:31]([Cl:32])=[CH:30][CH:29]=[CH:28][C:27]=1[N:33]1[CH2:38][CH2:37][N:36]([CH2:2][CH:3]2[CH2:8][CH2:7][CH:6]([CH2:9][O:10][C:11]3[CH:20]=[C:19]4[C:14]([CH2:15][CH2:16][C:17](=[O:21])[NH:18]4)=[CH:13][CH:12]=3)[CH2:5][CH2:4]2)[CH2:35][CH2:34]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 116303721-(2,3-Dichlorophenyl)piperazine hydrochlorideHCID 665595897-((4-(bromomethyl)cyclohexyl)methoxy)-3,4-dihydroquinolin-2(1H)-one

Product 1

HCID 565991467-((4-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)cyclohexyl)methoxy)-3,4-dihydroquinolin-2(1H)-oneYield 63%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of intermediate 49 (70 mg, 0.2 mmol) and NaI (60 mg, 0.4 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 41 (81 mg, 0.3 mmol) and anhydrous K2CO3 (110 mg, 0.8 mmol) were added to the mixture. The resulting mixture was heated to reflux and stirred for 4 h. 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=50:1) to give 7-((4-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)cyclohexyl)methoxy)-3,4-dihydroquinolin-2(1H)-one (compound 26) (63 mg, 63%). 1H NMR (300 MHz, CDCl3): δ 8.06 (s, 1H), 7.13-7.15 (m, 2H), 7.04 (d, J=8.4 Hz, 1H), 6.94-6.97 (m, 1H), 6.52 (dd, J=2.4 Hz, 8.4 Hz, 1H), 6.32 (d, J=2.1 Hz, 1H), 3.71-3.74 (m, 2H), 3.05-3.07 (m, 4H), 2.87-2.92 (m, 2H), 2.59-2.64 (m, 6H), 2.24 (d, J=6.9 Hz, 2H), 3.83 (d, J=9.9 Hz, 2H), 1.53-1.69 (m, 6H), 0.94-1.10 (m, 4H). HPLC: 99%, RT 2.652 min. MS (ESI) m/z 502.2 [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=50:1)

Sources & evidence

ORD record
ord-3f7af990001046e1890c5089742d3f21
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

Loading…