1H-Imidazo(4,5-c)pyridine → 1-(4-nitro-naphthalen-1-yl)-1H-imidazo[4,5-c]pyridine

HRID 2417004Notes

Reaction equation

HRID 2417004 reaction equation
[N:1]1[C:5]2[CH:6]=[CH:7][N:8]=[CH:9][C:4]=2[NH:3][CH:2]=1.CC(C)([O-])C.[K+].F[C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]([N+:27]([O-:29])=[O:28])=[CH:19][CH:18]=1>CS(C)=O>[N+:27]([C:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:17]([N:1]2[C:5]3[CH:6]=[CH:7][N:8]=[CH:9][C:4]=3[N:3]=[CH:2]2)=[CH:18][CH:19]=1)([O-:29])=[O:28]

Participants

5

Reactant 3

HCID 92271H-Imidazo(4,5-c)pyridineHCID 2617641-Fluoro-4-nitronaphthaleneHCID 23665647Potassium tert-butoxide

Product 1

HCID 226314061-(4-nitro-naphthalen-1-yl)-1H-imidazo[4,5-c]pyridine

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
60 °C

Procedure

5-Aza-benzimidazole (312 mg, 2.62 mmol, 1 equiv.) in 5 mL anhydrous DMSO was treated with potassium tert-butoxide (294 mg, 2.62 mmol, 1.0 equiv.) at room temperature. When the mixture was completely homogeneous, 4-fluoro-1-nitro-naphthalene (500 mg, 2.62 mmol, 1 equiv.) was added in one portion and the mixture was heated to 60° C. for 0.5 h. The reaction was allowed to cool, then quenched with dilute aqueous NaHCO3 solution. The product was extracted with a mixture of EtOAc, THF and acetone. The organic extracts were washed with water and brine, then dried (Na2SO4), filtered and the solvents removed in vacuo. 1H NMR revealed a 1:1 ratio of regioisomers. The products were purified by column chromatography on SiO2 using EtOAc/MeOH eluent mixtures. 1-(4-Nitro-naphthalen-1-yl)-1H-imidazo[5,4-c]pyridine was isolated at high Rf and 1-(4-nitro-naphthalen-1-yl)-1H-imidazo[4,5-c]pyridine at lower Rf, and overlapping fractions were in between. The overall yield was 357 mg (47%). Each nitro-naphthalene from above (˜100 mg, 0.4 mmol) was separately dissolved in 10 mL EtOAc and 5 mL of MeOH. Ammonium formate was then added (100 mg, 1.6 mmol or 4 equiv.) and 10% palladium-on-carbon (˜60 mg). The mixture was stirred for 0.5 h at 50° C., then allowed to cool, filtered through diatomaceous earth and the solvents were removed in vacuo to afford ˜80 mg of each naphthyl-amine 5a and 5b, which could be coupled with anilines or pyrazolamines to form ureas by the procedures described in Examples 2-4 above.

Workup

  1. temperatureto cool
  2. customquenched with dilute aqueous NaHCO3 solution
  3. extractionThe product was extracted with a mixture of EtOAc, THF and acetone
  4. washThe organic extracts were washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvents removed in vacuo
  8. customThe products were purified by column chromatography on SiO2

Sources & evidence

ORD record
ord-5a8a6e70808b403c9ee25e6c64ef11df
Source dataset
uspto-grants-2004_11
Patent number
US06825184B2

Reaction notes

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