Sodium Iodide → 8-(4-(4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy)butyl)piperazin-1-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one

HRID 1750146Notes

Reaction equation

HRID 1750146 reaction equation
ClC1C(Cl)=CC=CC=1N1CCCN([CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]2[CH:30]=[C:29]3[C:24]([CH:25]=[CH:26][C:27](=[O:31])[NH:28]3)=[CH:23][CH:22]=2)CC1.[Na+].[I-].[N:34]1([C:40]2[C:45]3[O:46][CH2:47][C:48](=[O:50])[NH:49][C:44]=3[CH:43]=[CH:42][CH:41]=2)[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1.C([O-])([O-])=O.[K+].[K+]>CC#N>[O:31]=[C:27]1[CH2:26][CH2:25][C:24]2[C:29](=[CH:30][C:21]([O:20][CH2:19][CH2:18][CH2:17][CH2:16][N:37]3[CH2:38][CH2:39][N:34]([C:40]4[C:45]5[O:46][CH2:47][C:48](=[O:50])[NH:49][C:44]=5[CH:43]=[CH:42][CH:41]=4)[CH2:35][CH2:36]3)=[CH:22][CH:23]=2)[NH:28]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 117156098-piperazin-1-yl-4H-benzo[1,4]oxazin-3-oneHCID 665595887-(4-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-one

Product 1

HCID 565979408-(4-(4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy)butyl)piperazin-1-yl)-2H-benzo[b][1,4]oxazin-3(4H)-oneYield 34%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of intermediate 4 (110 mg, 0.37 mmol) and NaI (110 mg, 0.74 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 59 (118 mg, 0.5 mmol) and anhydrous K2CO3 (138 mg, 1.92 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 8-(4-(4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy)butyl)piperazin-1-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (compound 38) (55 mg, 34%). 1H NMR (300 MHz, CDCl3): δ 10.56 (s, 1H), 9.96 (s, 1H), 7.04 (d, J=8.4 Hz, 1H), 6.85 (t, 1H), 6.57-6.43 (m, 4H), 4.53 (s, 2H), 3.92 (t, J=5.7 Hz, 2H), 2.97 (br, 4H), 2.78 (t, J=6.9 Hz, 2H), 2.43-2.38 (m, 4H), 1.72-1.58 (m, 4H). HPLC: 99%, RT 1.970 min. MS (ESI) m/z 451.0 [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-a3e209cade694f6290b89cfff7017967
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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