Sodium Iodide → HCID 86672721, compound

HRID 2369940Notes

Reaction equation

HRID 2369940 reaction equation
[CH:1]([C:3]1[C:11]2[C:10]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:8]=[CH:7][C:6]=2[NH:5][N:4]=1)=[O:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:22][O:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Br)=[CH:26][CH:25]=1.[I-].[Na+]>CN(C=O)C>[CH:1]([C:3]1[C:11]2[C:10]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:8]=[CH:7][C:6]=2[N:5]([CH2:28][C:27]2[CH:30]=[CH:31][C:24]([O:23][CH3:22])=[CH:25][CH:26]=2)[N:4]=1)=[O:2]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 1650214-Methoxybenzyl bromideHCID 178497600HCID 178497600, compound

Product 1

HCID 86672721HCID 86672721, compoundYield 53.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 3-formyl-1H-indazole-4-carboxylate (49.5 g, 242 mmol) was added cesium carbonate (158 g, 485 mmol) in DMF (750 mL) at 0° C. The mixture was stirred under an atmosphere of nitrogen for 15 min. To this solution were added 4-methoxybenzyl bromide (41.6 g, 267 mmol) and sodium iodide (7.3 g, 48.5 mmol). The resulting mixture continued to stir for 10 min and then warmed to room temperature and stirred for 2.5 h. The mixture was filtered to remove solid cesium carbonate and the filtrate was quenched with sat. aqueous sodium chloride (200 mL) and extracted with diethyl ether (3×500 mL). The combined organic layers were washed with brine (3×200 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, 10 to 25% ethyl acetate in hexanes) to afford methyl 3-formyl-1-(4-methoxybenzyl)-1H-indazole-4-carboxylate (41.8 g, 53%): 1H NMR δ (300 MHz, CDCl3) 10.53 (s, 1H), 7.77 (dd, J=7.2, 1.0 Hz, 1H), 7.58 (d, J=9.0, 1.0 Hz, 1H), 7.44 (dd, J=9.0, 7.20, Hz, 1H), 7.20 (dd, J=6.6, 2.1 Hz, 2H), 6.89 (dd, J=6.9, 2.1 Hz, 2H), 5.68 (s, 2H), 4.01 (s, 3H), 3.77 (s, 3H); MS (ESI+) m/z 325 (M+H). In addition, methyl 3-formyl-2-(4-methoxybenzyl)-2H-indazole-4-carboxylate (24.2 g, 31%) was also isolated: 1H NMR δ (300 MHz, CDCl3) 10.88 (s, 1H), 8.10 (t, J=7.2 Hz, 2H), 7.42 (dd, J=9.0, 1.0 Hz, 1H), 7.36 (dd, J=9.0, 7.20, Hz, 2H), 6.82 (dd, J=6.6, 2.1 Hz, 2H), 6.07 (s, 2H), 4.01 (s, 3H), 3.77 (s, 3H); MS (ESI+) m/z 325 (M+H).

Workup

  1. stirringto stir for 10 min
  2. stirringstirred for 2.5 h
  3. filtrationThe mixture was filtered
  4. customto remove solid cesium carbonate
  5. customthe filtrate was quenched with sat. aqueous sodium chloride (200 mL)
  6. extractionextracted with diethyl ether (3×500 mL)
  7. washThe combined organic layers were washed with brine (3×200 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude material was purified by column chromatography (silica gel, 10 to 25% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-0d4662673bed47ae9f69920fa5f3dff4
Source dataset
uspto-grants-2014_04
Patent number
US08710046B2

Reaction notes

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