HCID 89545449, compound → HCID 136508799, compound

HRID 2203403Notes

Reaction equation

HRID 2203403 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:18])=[C:6]([CH:17]=1)[C:7]([NH:9][CH2:10][C:11]1[CH:16]=[N:15][CH:14]=[CH:13][N:12]=1)=O>ClCCCl.P(Cl)(Cl)(Cl)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:18])=[C:6]([C:7]2[N:12]3[CH:13]=[CH:14][N:15]=[CH:16][C:11]3=[CH:10][N:9]=2)[CH:17]=1

Participants

4

Reactant 1

HCID 89545449HCID 89545449, compound

Product 1

HCID 136508799HCID 136508799, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 24813Phosphorus oxychlorideSolvent

Procedure

A suspension of 5-chloro-2-hydroxy-N-(pyrazin-2-ylmethyl)benzamide (0.38 g, 1.4 mmol) in a mixture of 1,2-dichloroethane (6 mL) and phosphoryl chloride (6 mL) was heated at reflux for 2 h, allowed to cool to ambient temperature and concentrated in vacuo. The residue was suspended in water (10 mL), and the pH was adjusted to 6-7 with 1 N aqueous sodium hydroxide. The aqueous phase was extracted with ethyl acetate (3×30 mL) followed by dichloromethane (3×40 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with a 0-10% gradient of methanol in dichloromethane to afford 4-chloro-2-(imidazo[1,5-a]pyrazin-3-yl)phenol as a pale yellow solid in 18% yield (0.064 g): MS (ES+) m/z 245.9 (M+1), 247.9 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. concentrationconcentrated in vacuo
  4. extractionThe aqueous phase was extracted with ethyl acetate (3×30 mL)
  5. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography
  9. washeluting with a 0-10% gradient of methanol in dichloromethane

Sources & evidence

ORD record
ord-011cb7a6873640648bd0c4f023eb1d9b
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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