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

HRID 1750107Notes

Reaction equation

HRID 1750107 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-].Cl.[CH:34]([O:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[N:44]1[CH2:50][CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1)([CH3:36])[CH3:35].[C:51]([O-])([O-])=O.[K+].[K+]>CC#N.O>[CH:34]([O:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[N:44]1[CH2:50][CH2:49][CH2:48][N:47]([CH2:51][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)[CH2:46][CH2:45]1)([CH3:36])[CH3:35]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 565980747-(3-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)propoxy)quinolin-2(1H)-oneHCID 666318431-(2-Isopropoxyphenyl)-1,4-diazepane hydrochloride

Product 1

HCID 565990117-(4-(4-(2-isopropoxyphenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-oneYield 62.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 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 34 (111 mg, 0.41 mmol) and anhydrous K2CO3 (226 mg, 1.64 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)quinolin-2(1H)-one (compound 18) (115 mg, 62%). 1H NMR (300 MHz, CDCl3) δ 11.68 (bs., 1H), 7.71 (d, J=9.3 Hz, 1H), 7.44 (d, J=9.3 Hz, 1H), 6.89-6.79 (m, 6H), 6.53 (d, J=9.6 Hz, 1H), 4.62-4.54 (m, 1H), 4.11-4.07 (m, 2H), 3.34-3.29 (m, 4H), 2.94-2.86 (m, 4H), 2.72-2.62 (m, 2H), 2.12-1.96 (m, 2H), 1.87-1.76 (m, 4H), 1.35 (d, J=6.0 Hz, 6H). HPLC: 99%, RT 2.434 min. MS (ESI) m/z 450.3 [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-95d1d64a130747b7856b879c390c3564
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

Loading…