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

HRID 1750089Notes

Reaction equation

HRID 1750089 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH2:11][CH2:12][NH:13][C:14]2=[O:17])=[CH:9][CH:8]=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](CCCCOC2C=C3C(CCC(=O)N3)=CC=2)[CH2:30][CH2:29]1.C([O-])([O-])=O.[K+].[K+]>CC#N.O>[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]([CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]2[CH:16]=[C:15]3[C:10]([CH2:11][CH2:12][NH:13][C:14]3=[O:17])=[CH:9][CH:8]=2)[CH2:30][CH2:29]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 56597938Unc0006HCID 686269787-(4-Bromobutoxy)-3,4-dihydro-1(2h)-isoquinolinone

Product 1

HCID 565982107-(4-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)-3,4-dihydroisoquinolin-1(2H)-oneYield 68.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of intermediate 21 (100 mg, 0.34 mmol) and NaI (102 mg, 0.68 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 2 (144 mg, 0.51 mmol) and anhydrous K2CO3 (188 mg, 1.36 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-(4-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)-3,4-dihydroisoquinolin-1(2H)-one (compound 6) (107 mg, 68%). 1H NMR (300 MHz, CDCl3) δ 7.58 (s, 1H), 7.20-7.09 (m, 3H), 7.02-6.98 (m, 2H), 6.04 (br., 1H), 4.05 (t, J=6.6 Hz, 2H), 3.54-3.52 (m, 2H), 3.32-3.28 (m, 4H), 2.95-2.91 (m, 6H), 2.70-2.68 (m, 2H), 2.06-2.04 (m, 2H), 1.84-1.77 (m, 4H). HPLC: 99%, RT 2.676 min. MS (ESI) m/z 462.4 [M+H]+. mp: 86-88° 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-05842c3cb429463ea1937217a58b3f03
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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