Sodium Iodide → 7-(4-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-one

HRID 1750081Notes

Reaction equation

HRID 1750081 reaction equation
BrCCCCOC1C=C2C(C=CC(=O)N2)=CC=1.[Na+].[I-].[Cl:20][C:21]1[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:22]=1[N:28]1[CH2:34][CH2:33][CH2:32][N:31]([CH2:35][CH2:36][CH2:37][CH2:38][O:39][C:40]2[CH:49]=[C:48]3[C:43]([CH2:44][CH2:45][C:46](=[O:50])[NH:47]3)=[CH:42][CH:41]=2)[CH2:30][CH2:29]1.C([O-])([O-])=O.[K+].[K+]>CC#N>[Cl:20][C:21]1[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:22]=1[N:28]1[CH2:34][CH2:33][CH2:32][N:31]([CH2:35][CH2:36][CH2:37][CH2:38][O:39][C:40]2[CH:49]=[C:48]3[C:43]([CH:44]=[CH:45][C:46](=[O:50])[NH:47]3)=[CH:42][CH:41]=2)[CH2:30][CH2:29]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 107563157-(4-BROMOBUTOXY)-QUINOLINE-2(1H)-ONEHCID 56597938Unc0006

Product 1

HCID 665595887-(4-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-oneYield 26%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of intermediate 15 (120 mg, 0.41 mmol) and NaI (123 mg, 0.82 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 2 (175 mg, 0.62 mmol) and anhydrous K2CO3 (226 mg, 1.64 mmol) were added to the mixture. The resulting mixture was heated to reflux overnight. The mixture was evaporated under reduced pressure and 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-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-one (compound 4) (50 mg, 26%). 1H NMR (300 MHz, CDCl3) δ 11.54 (br., 1H), 7.71 (d, J=6.9 Hz, 1H) 7.44 (d, J=8.1 Hz, 1H), 7.09-7.07 (m, 2H), 7.01-6.97 (m, 1H), 6.82-6.78 (m, 2H), 6.53 (d, J=9.3 Hz, 1H), 4.10 (t, J=6.6 Hz, 2H), 3.30 (d, J=5.1 Hz, 4H), 2.87-2.81 (m, 4H), 2.62 (t, J=7.5 Hz, 2H), 2.01-1.99 (m, 2H), 1.92-1.82 (m, 2H), 1.76-1.68 (m, 2H). HPLC: 99%, RT 2.461 min. MS (ESI) m/z 460.2 [M+H]+. mp: 55-57° C.

Workup

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

Sources & evidence

ORD record
ord-7e1b8c4af1cf411cb56c15207b9e276a
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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