Sodium Iodide → 6-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-1H-indazole

HRID 1750130Notes

Reaction equation

HRID 1750130 reaction equation
Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]2SC=[N:11][C:10]=2[CH:14]=1.[Na+].[I-].Cl.[Cl:18][C:19]1[C:24]([Cl:25])=[CH:23][CH:22]=[CH:21][C:20]=1[N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.[C:32]([O-])([O-])=O.[K+].[K+].C[C:39]#[N:40]>>[Cl:18][C:19]1[C:24]([Cl:25])=[CH:23][CH:22]=[CH:21][C:20]=1[N:26]1[CH2:31][CH2:30][N:29]([CH2:32][CH2:2][CH2:3][CH2:4][O:5][C:6]2[CH:14]=[C:10]3[C:9]([CH:39]=[N:40][NH:11]3)=[CH:8][CH:7]=2)[CH2:28][CH2:27]1

Participants

6

Reactant 5

HCID 5238Sodium IodideHCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 116303721-(2,3-Dichlorophenyl)piperazine hydrochlorideHCID 666315515-(3-Bromopropoxy)benzo[d]thiazole

Product 1

HCID 565970916-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-1H-indazoleYield 35%

Procedure

A mixture of intermediate 51 (65 mg, 0.24 mmol) and NaI (72 mg, 0.48 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 41 (97 mg, 0.36 mmol) and anhydrous K2CO3 (132 mg, 0.96 mmol) were added to the mixture. The resulting mixture was heated to reflux and stirred overnight. 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 6-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-1H-indazole (compound 28) (35 mg, 35%). 1H NMR (300 MHz, CDCl3): δ 7.97 (s, 1H), 7.61 (d, J=8.7 Hz 1H), 7.17-7.15 (m, 2H), 6.96 (dd, J=3.0 Hz, 6.6 Hz, 1H), 6.86-6.81 (m, 2H), 4.05 (t, J=5.4 Hz, 2H), 3.16 (s, 4H), 2.79 (s, 4H), 2.64-2.60 (m, 2H), 1.89-1.83 (m, 4H). HPLC: 99%, RT 2.491 min. MS (ESI) m/z 419.2 [M+H]+. mp: 101-103° C.

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-a547b860643e4ee0a7828a842c5ff6a9
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

Loading…