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

HRID 1887404Notes

Reaction equation

HRID 1887404 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

Sources & evidence

ORD record
ord-e81266dce90c47e98ced2c8e0b016db9
Source dataset
uspto-grants-2013_08
Patent number
US08501755B2

Reaction notes

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