Sodium Iodide → 7-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one

HRID 1750142Notes

Reaction equation

HRID 1750142 reaction equation
C(OC1C=CC=CC=1N1CCCN([CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:31]=[C:30]3[C:25]([CH2:26][CH2:27][C:28](=[O:32])[NH:29]3)=[CH:24][CH:23]=2)CC1)C.[Na+].[I-].Cl.[CH3:36][O:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[N:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1.C([O-])([O-])=O.[K+].[K+]>CC#N>[CH3:36][O:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[N:44]1[CH2:49][CH2:48][N:47]([CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:31]=[C:30]3[C:25]([CH2:26][CH2:27][C:28](=[O:32])[NH:29]3)=[CH:24][CH:23]=2)[CH2:46][CH2:45]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 9899402N-(2-Methoxyphenyl)piperazine hydrochlorideHCID 565988787-(4-(4-(2-ethoxyphenyl)-1,4-diazepan-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one

Product 1

HCID 106928867-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-oneYield 60%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of intermediate 12 (314 mg, 0.48 mmol) and NaI (150 mg, 0.96 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 55 (228 mg, 0.48 mmol) and anhydrous K2CO3 (138 mg, 1.92 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=30:1) to give 7-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one (compound 37) (98 mg, 60%). 1H NMR (300 MHz, CDCl3): δ 7.55 (s, 1H), 7.35 (d, J=8.1 Hz, 1H), 7.02-6.85 (m, 3H), 6.37-6.34 (m, 1H), 4.29-4.20 (m, 2H), 3.86 (s, 3H), 3.11 (brs, 4H), 2.86 (t, J=6.9 Hz, 2H), 2.67-2.61 (m, 5H), 2.48 (t, J=7.2 Hz, 1H), 1.82-1.62 (m, 6H). HPLC: 99%, RT 2.109 min. MS (ESI) m/z 411.2 [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=30:1)

Sources & evidence

ORD record
ord-a4fdfb21870545d38dff2040327f23d5
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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