Sodium Iodide → 7-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)piperazin-1-yl)butoxy)-3,4-dihydro-1,8-naphthyridin-2(1H)-one

HRID 1750151Notes

Reaction equation

HRID 1750151 reaction equation
C(OC1C=CC=CC=1N1CCCN([CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2C=[C:30]3[C:25]([CH2:26][CH2:27][C:28](=[O:32])[NH:29]3)=[CH:24][CH:23]=2)CC1)C.[Na+].[I-].[O:35]1[CH2:40][CH2:39][O:38][C:37]2[C:41]([N:45]3[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]3)=[CH:42][CH:43]=[CH:44][C:36]1=2.C([O-])([O-])=O.[K+].[K+].CC#[N:59]>>[O:35]1[CH2:40][CH2:39][O:38][C:37]2[C:41]([N:45]3[CH2:46][CH2:47][N:48]([CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]4[N:59]=[C:30]5[C:25]([CH2:26][CH2:27][C:28](=[O:32])[NH:29]5)=[CH:24][CH:23]=4)[CH2:49][CH2:50]3)=[CH:42][CH:43]=[CH:44][C:36]1=2

Participants

6

Reactant 5

HCID 5238Sodium IodideHCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 65853EltoprazineHCID 565988787-(4-(4-(2-ethoxyphenyl)-1,4-diazepan-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one

Product 1

HCID 210735537-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)piperazin-1-yl)butoxy)-3,4-dihydro-1,8-naphthyridin-2(1H)-oneYield 83%

Procedure

A mixture of intermediate 12 (100 mg, 0.32 mmol) and NaI (95 mg, 0.64 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 61 (105 mg, 0.48 mmol) and anhydrous K2CO3 (176 mg, 1.27 mmol) were added to the mixture. The resulting mixture was heated to reflux and stirred for 4 h. Precipitated crystals were filtered off and the filtrate was evaporated under reduced pressure. The residue was 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-dihydrobenzo[b][1,4]dioxin-5-yl)piperazin-1-yl)butoxy)-3,4-dihydro-1,8-naphthyridin-2(1H)-one (compound 41) (115 mg, 83%). 1H NMR (300 MHz, CDCl3): δ 7.60 (s, 1H), 7.36 (d, J=8.1 Hz, 1H), 7.27 (s, 1H), 6.78 (t, J=8.1 Hz, 1H), 6.61-6.53 (m, 2H), 6.35 (d, J=8.1 Hz, 1H), 4.33-4.20 (m, 6H), 3.10 (s, 4H), 2.86 (dd, J=7.5 Hz, 2H), 2.67-2.62 (m, 6H), 2.51-2.46 (m, 2H), 1.82-1.69 (m, 6H). HPLC: 99%, RT 2.084 min. MS (ESI) m/z 439.2 [M+H]+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 30 min
  3. temperatureThe resulting mixture was heated
  4. temperatureto reflux
  5. customPrecipitated crystals
  6. filtrationwere filtered off
  7. customthe filtrate was evaporated under reduced pressure
  8. extractionThe residue was extracted with EtOAc
  9. washThe combined EtOAc layers were washed with brine
  10. dry with materialdried over anhydrous Na2SO4
  11. concentrationconcentrated in vacuo
  12. custompurified by flash chromatography on silica gel column (elution with DCM/MeOH=30:1)

Sources & evidence

ORD record
ord-ec1ebbeb92b5477e93a7949af28f2c04
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

Loading…