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

HRID 1750087Notes

Reaction equation

HRID 1750087 reaction equation
Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([CH2:10][CH2:11][NH:12][C:13]2=[O:16])=[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]([CH2:10][CH2:11][NH:12][C:13]3=[O:16])=[CH:8][CH:7]=2)[CH2:29][CH2:28]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 56597938Unc0006HCID 666321077-(3-bromopropoxy)-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 665595877-(3-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)propoxy)-3,4-dihydroisoquinolin-1(2H)-oneYield 71.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of intermediate 20 (110 mg, 0.39 mmol) and NaI (117 mg, 0.78 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 2 (165 mg, 0.58 mmol) and anhydrous K2CO3 (216 mg, 1.56 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)-3,4-dihydroisoquinolin-1(2H)-one (compound 5) (125 mg, 71%). 1H NMR (300 MHz, CDCl3) δ 7.60 (d, J=2.1 Hz, 1H), 7.14-7.08 (m, 3H), 7.02-7.00 (m, 2H), 6.02 (br., 1H), 4.10 (t, J=6.3 Hz, 2H), 3.56-3.53 (m, 2H), 3.31-3.27 (m, 4H), 2.96-2.88 (m, 6H), 2.77-2.72 (m, 2H), 2.01 (m, 4H). HPLC: 99%, RT 2.578 min. MS (ESI) m/z 448.1 [M+H]+. mp: 116-117° 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-a9805980f9b64f8c8167571a3d42f7bb
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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