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

HRID 1750103Notes

Reaction equation

HRID 1750103 reaction equation
Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([CH:10]=[CH:11][C:12](=[O:16])[NH:13]2)=[CH:8][CH:7]=1.[Na+].[I-].[Cl:19][C:20]1[C:25]([Cl:26])=[CH:24][CH:23]=[CH:22][C:21]=1[N:27]1[CH2:33][CH2:32][CH2:31][N:30](CCCCOC2C=C3C(CCC(=O)N3)=CC=2)[CH2:29][CH2:28]1.C([O-])([O-])=O.[K+].[K+]>CC#N.O>[Cl:19][C:20]1[C:25]([Cl:26])=[CH:24][CH:23]=[CH:22][C:21]=1[N:27]1[CH2:33][CH2:32][CH2:31][N:30]([CH2:2][CH2:3][CH2:4][O:5][C:6]2[CH:15]=[C:14]3[C:9]([CH:10]=[CH:11][C:12](=[O:16])[NH:13]3)=[CH:8][CH:7]=2)[CH2:29][CH2:28]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 299750407-(3-bromopropoxy)quinolin-2(1H)-oneHCID 56597938Unc0006

Product 1

HCID 565980747-(3-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)propoxy)quinolin-2(1H)-oneYield 39.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of intermediate 32 (217 mg, 0.77 mmol) and NaI (231 mg, 1.54 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 2 (217 mg, 0.77 mmol) and anhydrous K2CO3 (425 mg, 3.08 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=30:1) to give 7-(3-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)propoxy)quinolin-2(1H)-one (compound 15) (135 mg, 39%). 1H NMR (300 MHz, CDCl3) δ 11.96 (bs., 1H), 7.72 (d, J=9.3 Hz, 1H) 7.45 (d, J=8.7 Hz, 1H), 7.09-7.07 (m, 2H), 7.01-6.99 (m, 1H), 6.83-6.81 (m, 2H), 6.54 (d, J=9.0 Hz, 1H), 4.15 (t, J=5.7 Hz, 2H), 3.31 (d, J=5.1 Hz, 4H), 2.92-2.96 (m, 4H), 2.76 (t, J=6.6 Hz, 2H), 2.03-1.01 (m, 4H). HPLC: 99%, RT 2.348 min. MS (ESI) m/z 446.1 [M+H]+. mp: 117-118° C.

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=30:1)

Sources & evidence

ORD record
ord-b12996cc42564bfeb8626343064d8b6e
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

Loading…