Picolinic acid → 2-(3-(1H-indazol-1-yl)phenoxy)-9-(pyridin-2-yl)-9H-carbazole

HRID 1050639Notes

Reaction equation

HRID 1050639 reaction equation
[N:1]1([C:10]2[CH:11]=[C:12]([OH:16])[CH:13]=[CH:14][CH:15]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1.Br[C:18]1[CH:30]=[CH:29][C:28]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=3)[C:20]=2[CH:19]=1.N1C=CC=CC=1C(O)=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>[Cu]I>[N:1]1([C:10]2[CH:11]=[C:12]([CH:13]=[CH:14][CH:15]=2)[O:16][C:18]2[CH:30]=[CH:29][C:28]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[N:21]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=4)[C:20]=3[CH:19]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1

Participants

6

Reactant 4

HCID 1018Picolinic acidHCID 62657Potassium Phosphate, TribasicHCID 644360733-(1H-indazol-1-yl)phenolHCID 706548522-bromo-9-(pyridin-2-yl)-9H-carbazole

Product 1

HCID 1180074432-(3-(1H-indazol-1-yl)phenoxy)-9-(pyridin-2-yl)-9H-carbazoleYield 88%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
95 °C

Procedure

To a dry Shlenck tube equipped with a magnetic stir bar was added 3-(1H-indazol-1-yl)phenol 2 (630 mg, 3.0 mmol, 1.0 eq), 2-bromo-9-(pyridin-2-yl)-9H-carbazole (1163 mg, 3.6 mmol, 1.2 eq), CuI (57 mg, 0.3 mmol, 0.1 eq), picolinic acid (74 mg, 0.6 mmol, 0.2 eq) and K3PO4 (1273 mg, 6.0 mmol, 2.0 eq). The tube was evacuated and backfilled with nitrogen. The evacuation and backfill procedure was repeated for another twice. Then solvent DMSO (9 mL) was added under the protection of nitrogen. The mixture was stirred in an oil bath at a temperature of 90-100° C. for 3 days and then cooled down to ambient temperature. Water was added to dissolve the solid. The mixture was extracted with ethyl acetate three times. The combined organic layer was washed with water three time, dried over sodium sulfate, and then filtered. The solvent was removed under reduced pressure, and the residue was purified through column chromatography on silica gel using hexane/ethyl acetate (10:1-5:1-3:1) as eluent to obtain the desired product Ligand ON12 as a colorless solid 1200 mg in 88% yield. 1H NMR (DMSO-d6, 400 MHz): δ 7.05-7.08 (m, 1H), 7.15 (dd, J=8.4, 2.0 Hz, 1H), 7.24 (t, J=8.0 Hz, 1H), 7.32-7.36 (m, 2H), 7.42-7.47 (m, 3H), 7.52-7.59 (m, 2H), 7.61 (d, J=2.0 Hz, 1H), 7.77-7.83 (m, 3H), 7.86 (d, J=8.0 Hz, 1H), 8.07 (td, J=7.6, 2.0 Hz, 1H), 8.23 (d, J=7.6 Hz, 1H), 8.29 (d, J=7.6 Hz, 1H), 8.33 (s, 1H), 8.66 (dd, J=5.2, 1.6 Hz, 1H). 13C NMR (DMSO-d6, 100 MHz): δ 102.73, 110.40, 111.12, 113.54, 115.66, 116.09, 119.05, 120.28, 120.22, 121.26, 121.56, 121.82, 122.12, 123.24, 125.16, 126.02, 127.64, 131.09, 136.02, 138.01, 139.35, 139.53, 139.94, 140.98, 149.52, 150.45, 154.58, 158.62.

Workup

  1. customTo a dry Shlenck tube equipped with a magnetic stir bar
  2. customThe tube was evacuated
  3. additionThen solvent DMSO (9 mL) was added under the protection of nitrogen
  4. temperaturecooled down to ambient temperature
  5. additionWater was added
  6. dissolutionto dissolve the solid
  7. extractionThe mixture was extracted with ethyl acetate three times
  8. washThe combined organic layer was washed with water three time
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customThe solvent was removed under reduced pressure
  12. customthe residue was purified through column chromatography on silica gel

Sources & evidence

ORD record
ord-97d4a010ba964bf684ee49ff6cf0feac
Source dataset
uspto-grants-2016_07
Patent number
US09385329B2

Reaction notes

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