5-Nitroindazole → 1-(3-fluorobenzyl)-5-nitro-1H-indazole

HRID 2105295Notes

Reaction equation

HRID 2105295 reaction equation
[H-].[Na+].[N+:3]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][N:10]=[CH:9]2)([O-:5])=[O:4].Br[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=1>CN(C=O)C>[F:23][C:19]1[CH:18]=[C:17]([CH:22]=[CH:21][CH:20]=1)[CH2:16][N:11]1[C:12]2[C:8](=[CH:7][C:6]([N+:3]([O-:5])=[O:4])=[CH:14][CH:13]=2)[CH:9]=[N:10]1

Participants

5

Reactant 3

HCID 215015-NitroindazoleHCID 24758Sodium hydrideHCID 680073-Fluorobenzyl bromide

Product 1

HCID 219664901-(3-fluorobenzyl)-5-nitro-1H-indazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (NaH) 95% (0.81 g, 34.1 mmol) was added to a solution of 5-nitro-1H-indazole Compound 4a (5.3 g, 32.5 mmol) in DMF (33 mL) at 0° C. under nitrogen. The mixture was stirred for 1 hour at RT, then 1-bromomethyl-3-fluoro-benzene Compound 4b (6.14 g, 32.5 mmol) was added dropwise at 0° C. After stirring at RT for 12 hours, the reaction mixture was partitioned between ethyl acetate and icy water. The organic layer washed with water, brine, dried (Na2SO4), filtered and the solvent evaporated in vacuo to yield a crude solid. The crude solid was purified via flash chromatography (100% dichloromethane) to yield 1-(3-fluoro-benzyl)-5-nitro-1H-indazole Compound 4c (4.02 g, 46%) as a solid. 1H NMR (400 MHz, CDCl3) δ 8.76-8.75 (1H, m), 8.27-8.23 (2H, m), 7.40-7.38 (1H, m), 7.33-2.27 (1H, m), 7.01-6.97 (2H, m), 6.89-6.86 (1H, m), 5.64 (2H, s); MS (ES+) m/z 272.1 (MH+).

Workup

  1. stirringAfter stirring at RT for 12 hours
  2. customthe reaction mixture was partitioned between ethyl acetate and icy water
  3. washThe organic layer washed with water, brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvent evaporated in vacuo
  7. customto yield a crude solid
  8. customThe crude solid was purified via flash chromatography (100% dichloromethane)

Sources & evidence

ORD record
ord-ac24b349f2244640984eb15591d69d22
Source dataset
uspto-grants-2009_08
Patent number
US07579356B2

Reaction notes

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