Potassium Carbonate → 2-[(3-Fluorophenyl)methyl]-5-nitroindazole

HRID 2353817Notes

Reaction equation

HRID 2353817 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[CH:7]2)([O-:3])=[O:2].[F:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH2:17]Br.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:17][C:16]1[CH:19]=[CH:20][CH:21]=[C:14]([F:13])[CH:15]=1)[N:8]=[CH:7]2)([O-:3])=[O:2].[N+:1]([C:4]1[CH:12]=[CH:11][C:10]2[C:6](=[CH:7][N:8]([CH2:17][C:16]3[CH:19]=[CH:20][CH:21]=[C:14]([F:13])[CH:15]=3)[N:9]=2)[CH:5]=1)([O-:3])=[O:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 215015-NitroindazoleHCID 680073-Fluorobenzyl bromide

Product 2

HCID 210494212-[(3-Fluorophenyl)methyl]-5-nitroindazoleYield 37%HCID 219664901-(3-fluorobenzyl)-5-nitro-1H-indazoleYield 32%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

5-nitroindazole (15 g, 92 mmol, 1 eq), 3-fluorobenzylbromide (14.7 mL, 119.5 mmol, 1.3 eq) and potassium carbonate 25.4 g (184 mmol, 2 equiv) were suspended in 150 mL acetonitrile. The reaction mixture was stirred at 70° C. for 12 h, and then allowed to cool to rt. The resultant solid was filtered and washed with CH2Cl2, and the filtrate concentrated in vacuo. The crude mixture of regioisomeric products was purified by column chromatography (5:1 to 4:1 Hex/EtOAc), yielding 5-nitro-1-N-(3-fluorobenzyl)indazole (7.9 g, 32%) and 5-nitro-2-N-(3-fluorobenzyl) indazole (9.2 g, 37%) as yellow solids.

Workup

  1. temperatureto cool to rt
  2. filtrationThe resultant solid was filtered
  3. washwashed with CH2Cl2
  4. concentrationthe filtrate concentrated in vacuo
  5. additionThe crude mixture of regioisomeric products
  6. customwas purified by column chromatography (5:1 to 4:1 Hex/EtOAc)

Sources & evidence

ORD record
ord-29944860ff5348f7a4e09c1fd28c923f
Source dataset
uspto-grants-2010_07
Patent number
US07750017B2

Reaction notes

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