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

HRID 1750101Notes

Reaction equation

HRID 1750101 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[CH:12][C:13](=[O:17])[NH:14]2)=[CH:9][CH:8]=1.[Na+].[I-].Cl.[CH2:21]([O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[N:30]1[CH2:36][CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)[CH3:22].C([O-])([O-])=O.[K+].[K+]>CC#N.O>[CH2:21]([O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[N:30]1[CH2:36][CH2:35][CH2:34][N:33]([CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]2[CH:16]=[C:15]3[C:10]([CH:11]=[CH:12][C:13](=[O:17])[NH:14]3)=[CH:9][CH:8]=2)[CH2:32][CH2:31]1)[CH3:22]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 107563157-(4-BROMOBUTOXY)-QUINOLINE-2(1H)-ONEHCID 666337571-(2-Ethoxyphenyl)-1,4-diazepane hydrochloride

Product 1

HCID 666335847-(4-(4-(2-ethoxyphenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-oneYield 24%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of intermediate 15 (150 mg, 0.51 mmol) and NaI (150 mg, 1.0 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 31 (130 mg, 0.51 mmol) and anhydrous K2CO3 (282 mg, 2.04 mmol) were added to the mixture. The resulting mixture was heated to reflux and stirred overnight. The reaction solution was diluted with water and 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-ethoxyphenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-one (compound 14) (50 mg, 24%). 1H NMR (300 MHz, CDCl3) δ 10.89 (bs, 1H), 7.69 (d, J=9.6 Hz, 1H), 7.44 (d, J=9.0 Hz, 1H), 6.92-6.78 (m, 5H), 6.71 (d, J=2.7 Hz, 1H), 6.51 (d, J=9.6 Hz, 1H), 4.10-4.01 (m, 4H), 3.36-3.30 (m, 4H), 2.89-2.79 (m, 4H), 2.62-2.59 (m, 4H), 2.02-2.01 (m, 2H), 1.89-1.82 (m, 2H), 1.45 (t, J=6.9 Hz, 3H). HPLC: 99%, RT 2.375 min. MS (ESI) m/z 436.2 [M+H]+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 30 min
  3. temperatureThe resulting mixture was heated
  4. temperatureto reflux
  5. extractionextracted with EtOAc
  6. washThe combined EtOAc layers were washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated in vacuo
  9. custompurified by flash chromatography on silica gel column (elution with DCM/MeOH=50:1)

Sources & evidence

ORD record
ord-5681556f8bed4cfca17a5f6a0bc9ef23
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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