Phosphorus oxychloride → 6-Chloro-3-(3,3,4,4,4-pentafluorobutyl)imidazo[1,5-a]pyridine

HRID 2203341Notes

Reaction equation

HRID 2203341 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][NH:9][C:10](=O)[CH2:11][CH2:12][C:13]([F:19])([F:18])[C:14]([F:17])([F:16])[F:15])=[N:6][CH:7]=1.P(Cl)(Cl)(Cl)=O>ClCCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:10]([CH2:11][CH2:12][C:13]([F:19])([F:18])[C:14]([F:17])([F:16])[F:15])=[N:9][CH:8]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 86678976N-[(5-chloropyridin-2-yl)methyl]-4,4,5,5,5-pentafluoropentanamide

Product 1

HCID 866789776-Chloro-3-(3,3,4,4,4-pentafluorobutyl)imidazo[1,5-a]pyridine

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of the intermediate from Step F (7.1 g, 22.42 mmol) in 1,2-dichloroethane (30 mL) was added phosphorous oxychloride (10.45 mL, 112 mmol). The resulting mixture was refluxed for 18 hours. The reaction mixture was cooled to room temperature and concentrated. The residue was partitioned between water and ethyl acetate. The aqueous layer was neutralized with solid sodium bicarbonate and then extracted with ethyl acetate (3×). The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography using a hexanes/EtOAc gradient to give a light yellow solid. m/z=298.9 (M+H).

Workup

  1. temperatureThe resulting mixture was refluxed for 18 hours
  2. concentrationconcentrated
  3. customThe residue was partitioned between water and ethyl acetate
  4. extractionextracted with ethyl acetate (3×)
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography
  10. customto give a light yellow solid

Sources & evidence

ORD record
ord-b97cc0b68b9c43ed8b57d97fd0bd4b12
Source dataset
uspto-grants-2016_06
Patent number
US09365574B2

Reaction notes

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