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

HRID 1750155Notes

Reaction equation

HRID 1750155 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:17][C:18]1[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][C:19]=1[CH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.C[CH2:32][N:33](C(C)C)C(C)C.[CH3:40]C#N>>[Cl:17][C:18]1[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][C:19]=1[CH:25]1[CH2:30][CH2:29][N:28]([CH2:40][CH2:2][CH2:3][CH2:4][O:5][C:6]2[CH:14]=[C:10]3[C:9]([CH:32]=[N:33][NH:11]3)=[CH:8][CH:7]=2)[CH2:27][CH2:26]1

Participants

6

Reactant 5

HCID 5238Sodium IodideHCID 6342AcetonitrileHCID 81531DiisopropylethylamineHCID 17895683HCID 17895683, compoundHCID 666315515-(3-Bromopropoxy)benzo[d]thiazole

Product 1

HCID 565972286-(4-(4-(2,3-dichlorophenyl)piperidin-1-yl)butoxy)-1H-indazoleYield 60%

Procedure

A mixture of intermediate 51 (40.6 mg, 0.15 mmol) and NaI (45.2 mg, 0.30 mmol) in CH3CN (3 mL) was heated to reflux for 30 min and then cooled to rt. To this mixture was added intermediate 47 (60.3 mg, 0.23 mmol), followed then by DIEA (0.058 mL, 0.33 mmol). 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 ISCO to give 6-(4-(4-(2,3-dichlorophenyl)piperidin-1-yl)butoxy)-1H-indazole (compound 45) (37.6 mg, 60%). 1H NMR (400 MHz, CDCl3): δ 7.93 (s, 1H), 7.54 (d, J=8.8 Hz, 1H), 7.33 (dd, J=7.9, 1.2 Hz, 1H), 7.25-7.20 (m, 1H), 7.15 (t, J=7.9 Hz, 1H), 6.93 (s, 1H), 6.74 (dd, J=8.8, 1.9 Hz, 1H), 3.94 (t, J=6.0 Hz, 2H), 3.75-3.67 (m, 2H), 3.46-3.36 (m, 1H), 3.15-3.08 (m, 2H), 3.03-2.91 (m, 2H), 2.59-2.43 (m, 2H), 2.18-2.06 (m, 2H), 2.06-1.96 (m, 2H), 1.88-1.75 (m, 2H). HPLC: 99%, RT 4.447 min. MS (ESI) m/z 418.10 [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 ISCO

Sources & evidence

ORD record
ord-4e7845de19fd48288e76a681056a4153
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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