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

HRID 1750105Notes

Reaction equation

HRID 1750105 reaction equation
Cl[C:2]1[C:7](Cl)=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[CH2:15][CH2:14][CH2:13][N:12]([CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]2[CH:30]=[C:29]3[C:24]([CH:25]=[CH:26][C:27](=[O:31])[NH:28]3)=[CH:23][CH:22]=2)[CH2:11][CH2:10]1.[Na+].[I-].Cl.[CH:35]([O:38]C1C=CC=CC=1N1CCCNCC1)([CH3:37])[CH3:36].C([O-])([O-])=O.[K+].[K+]>CC#N.O>[CH:35]([O:38][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[CH2:15][CH2:14][CH2:13][N:12]([CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]2[CH:30]=[C:29]3[C:24]([CH2:25][CH2:26][C:27](=[O:31])[NH:28]3)=[CH:23][CH:22]=2)[CH2:11][CH2:10]1)([CH3:37])[CH3:36]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 665595887-(4-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-oneHCID 666318431-(2-Isopropoxyphenyl)-1,4-diazepane hydrochloride

Product 1

HCID 565980757-(4-(4-(2-isopropoxyphenyl)-1,4-diazepan-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-oneYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of intermediate 4 (75 mg, 0.25 mmol) and NaI (75 mg, 0.5 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 34 (100 mg, 0.37 mmol) and anhydrous K2CO3 (138 mg, 1.0 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-isopropoxyphenyl)-1,4-diazepan-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one (compound 16) (81 mg, 72%). 1H NMR (300 MHz, CDCl3) δ 7.72 (bs, 1H), 7.03 (d, J=8.1 Hz, 1H), 6.89-6.85 (m, 4H), 6.51 (d, J=8.1 Hz, 1H), 6.30 (s, 1H), 4.62-4.57 (m, 1H), 4.02-3.92 (m, 2H), 3.42-3.36 (m, 2H), 3.32-3.28 (m, 2H), 3.07-3.00 (m, 4H), 2.89 (t, J=7.2 Hz, 2H), 2.80-2.74 (m, 2H), 2.61 (t, J=6.9 Hz, 2H), 2.20-2.10 (m, 2H), 1.90-1.76 (m, 4H), 1.35 (d, J=6.0 Hz, 6H). HPLC: 99%, RT 2.506 min. MS (ESI) m/z 452.4 [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-1d6f1d8f496046229af49058918f4b05
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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