4-Aminopyridine → 2,6-dichloro-4-iodo-N-(pyridin-4-yl)benzamide

HRID 449873Notes

Reaction equation

HRID 449873 reaction equation
S(Cl)(Cl)=O.[Cl:5][C:6]1[CH:14]=[C:13]([I:15])[CH:12]=[C:11]([Cl:16])[C:7]=1[C:8]([OH:10])=O.[NH2:17][C:18]1[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=1.C(N(CC)CC)C>C1COCC1>[Cl:16][C:11]1[CH:12]=[C:13]([I:15])[CH:14]=[C:6]([Cl:5])[C:7]=1[C:8]([NH:17][C:18]1[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=1)=[O:10]

Participants

6

Reactant 4

HCID 17274-AminopyridineHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 513418772,6-Dichloro-4-iodobenzoic acid

Product 1

HCID 596180002,6-dichloro-4-iodo-N-(pyridin-4-yl)benzamideYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Thionyl chloride (20 mL) was added to 2,6-dichloro-4-iodobenzoic acid (1.5 g, 4.73 mmol) and the mixture was heated to reflux for 5 h under nitrogen. After cooling the mixture was concentrated under reduced pressue. Toluene (10 mL) was added and the mixture was concentrated under reduced pressure again to remove residual thionyl chloride. The residue was dissolved in anhydrous THF (20 mL) and this was added dropwise to a cooled (0° C.) solution of 4-aminopyridine (0.53 g, 5.68 mmol) and triethylamine (1.32 mL, 9.46 mmol) in anhydrous THF (20 mL). After addition was complete, the mixture was stirred at room temperature under nitrogen overnight. The reaction was poured onto the ice water (50 mL) and extracted with EtOAc (2×50 mL). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hexanes/EtOAc=3:1) to afford the desired product (1.8 g, yield: 97%.) 1HNMR (DMSO-d6, 400 MHz): 611.14 (s, 1H), 8.47 (dd, J=1.6, 4.8 Hz, 2H), 8.03 (d, J=2.0 Hz, 2H), 7.59 (dd, J=1.6, 4.8 Hz, 2H). LCMS (ESI) m/z: 393.0 [M+H+].

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 5 h under nitrogen
  3. temperatureAfter cooling the mixture
  4. concentrationwas concentrated under reduced pressue
  5. additionToluene (10 mL) was added
  6. concentrationthe mixture was concentrated under reduced pressure again
  7. customto remove residual thionyl chloride
  8. dissolutionThe residue was dissolved in anhydrous THF (20 mL)
  9. additionthis was added dropwise to
  10. additionAfter addition
  11. extractionextracted with EtOAc (2×50 mL)
  12. dry with materialThe combined organic extracts were dried over sodium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (Hexanes/EtOAc=3:1)

Sources & evidence

ORD record
ord-c28c0fc2b56f45e28c7fc15aaf017256
Source dataset
uspto-grants-2013_07
Patent number
US08486950B2

Reaction notes

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