2-Chloronicotinic acid → 2-(2-Chloropyridin-3-YL)-5,6-difluoro-1H-benzo[D]imidazole

HRID 1875720Notes

Reaction equation

HRID 1875720 reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](O)=O.[F:11][C:12]1[CH:13]=[C:14]([NH2:20])[C:15]([NH2:19])=[CH:16][C:17]=1[F:18]>>[Cl:1][C:2]1[C:3]([C:4]2[NH:19][C:15]3[CH:16]=[C:17]([F:18])[C:12]([F:11])=[CH:13][C:14]=3[N:20]=2)=[CH:7][CH:8]=[CH:9][N:10]=1

Participants

3

Reactant 2

HCID 762582-Chloronicotinic acidHCID 27367551,2-Diamino-4,5-difluorobenzene

Product 1

HCID 717418032-(2-Chloropyridin-3-YL)-5,6-difluoro-1H-benzo[D]imidazoleYield 48%

Conditions

Temperature
180 °C

Procedure

To a suspension of 2-chloro-nicotinic acid (4.10 g, 0.026 mol; CAS Reg. No. 2942-59-8) in polyphosphoric acid (50 g) was added 4,5-difluoro-benzene-1,2-diamine (3.86 g, 0.026 mol; CAS Reg. No. 76179-40-3) and the resulting mixture was heated to 180° C. for 1 h. The reaction mixture was then cooled and neutralized with ice cold 10% aqueous sodium carbonate solution, and then extracted with ethyl acetate. The combined organic layer was dried over sodium sulfate, filtered, and evaporated under reduced pressure. The crude residue thus obtained was purified by column chromatography over silica gel (25% ethyl acetate/n-hexane) to give the title compound as a brown solid (48%). MS (Turbo Spray): m/z=266.1 (M+H).

Workup

  1. temperatureThe reaction mixture was then cooled
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe crude residue thus obtained
  7. customwas purified by column chromatography over silica gel (25% ethyl acetate/n-hexane)

Sources & evidence

ORD record
ord-66684b27e5e5476aaf7d2b8bd545f6cb
Source dataset
uspto-grants-2012_11
Patent number
US08309581B2

Reaction notes

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