Sodium Iodide → 7-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one

HRID 1750152Notes

Reaction equation

HRID 1750152 reaction equation
ClC1C(Cl)=CC=CC=1N1CCCN([CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:29]=[C:28]3[C:23]([CH:24]=[CH:25][C:26](=[O:30])[NH:27]3)=[CH:22][CH:21]=2)CC1.[Na+].[I-].[O:33]1[CH2:38][CH2:37][O:36][C:35]2[C:39]([N:43]3[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]3)=[CH:40][CH:41]=[CH:42][C:34]1=2.[C:49]([O-])([O-])=O.[K+].[K+]>CC#N>[O:33]1[CH2:38][CH2:37][O:36][C:35]2[C:39]([N:43]3[CH2:44][CH2:45][N:46]([CH2:49][CH2:16][CH2:17][CH2:18][O:19][C:20]4[CH:29]=[C:28]5[C:23]([CH:24]=[CH:25][C:26](=[O:30])[NH:27]5)=[CH:22][CH:21]=4)[CH2:47][CH2:48]3)=[CH:40][CH:41]=[CH:42][C:34]1=2

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 65853EltoprazineHCID 565980747-(3-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)propoxy)quinolin-2(1H)-one

Product 1

HCID 666336627-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-oneYield 50%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of intermediate 15 (70 mg, 0.24 mmol) and NaI (70 mg, 0.48 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 61 (78 mg, 0.36 mmol) and anhydrous K2CO3 (162 mg, 0.96 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 EtOA. 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-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)piperazin-1-yl)butoxy)quinolin-2(1H)-one (compound 42) (52 mg, 50%). 1H NMR (300 MHz, CDCl3): δ 11.65 (brs, 1H), 7.72 (d, J=9.6 Hz, 1H), 7.45 (d, J=8.4 Hz, 1H), 6.82-6.75 (m, 3H), 6.61-6.52 (m, 3H), 4.33-4.26 (m, 4H), 4.12-4.08 (m, 2H), 3.12 (br, 4H), 2.70 (br, 4H), 2.52 (br, 2H), 2.04-1.68 (m, 6H). HPLC: 99%, RT 2.167 min. MS (ESI) m/z 436.0 [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 EtOA
  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-f296e42f77b0488ba565cbdc95d68444
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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