Hydrochloric Acid → Irampanel

HRID 650983Notes

Reaction equation

HRID 650983 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:12][N:11]=[C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:9]=1.[H-].[Na+].Cl.[CH3:22][N:23]([CH2:25][CH2:26]Cl)[CH3:24].Cl>O1CCOCC1.C(O)C>[CH3:22][N:23]([CH2:25][CH2:26][O:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:12][N:11]=[C:10]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:9]=1)[CH3:24]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydride2×HCID 77919279349-24-9HCID 11636816N,N-Dimethylaminoethyl chloride hydrochloride

Product 1

HCID 3038472Irampanel

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
27.5 °C

Procedure

2.38 g of 5-(2-hydroxyphenyl)-3-phenyl-1,2,4-oxadiazole are dissolved in 100 ml of anhydrous dioxane and stirred with 0.3 g of 80% sodium hydride suspension in oil for 15 minutes at 25-30° C. To this solution is added 60 ml of anhydrous dioxane, the resulting mixture is combined with 2.88 g of 2-(N,N-dimethylamino)ethylchloride hydrochloride and 0.6 g of 80% sodium hydride suspension in oil. This solution is also stirred for 15 minutes at 25-30° C. The combined solutions are refluxed for 8 hours, left to stand overnight and evaporated down in vacuo. The residue is mixed with water and 20 ml of 1N sodium hydroxide solution and extracted with ethyl acetate. The organic phase is dried over sodium sulphate, the solvent evaporated in vacuo and the residue chromatographed on silica gel with ethyl acetate/isopropanol (70:30, mixed with 2.5% of a 25% ammonia solution). The base thus obtained is dissolved in anhydrous ethanol, acidified with ethereal HCl and precipitated with diethyl ether. The residue is recrystallised from anhydrous ethanol and diethylether. Yield: 2.2 g (64% of theory). m.p.: 186-187° C.

Workup

  1. temperatureThe combined solutions are refluxed for 8 hours
  2. waitleft
  3. waitto stand overnight
  4. customevaporated down in vacuo
  5. additionThe residue is mixed with water and 20 ml of 1N sodium hydroxide solution
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic phase is dried over sodium sulphate
  8. customthe solvent evaporated in vacuo
  9. customthe residue chromatographed on silica gel with ethyl acetate/isopropanol (70:30
  10. additionmixed with 2.5% of a 25% ammonia solution)
  11. customThe base thus obtained
  12. customprecipitated with diethyl ether
  13. customThe residue is recrystallised from anhydrous ethanol and diethylether

Sources & evidence

ORD record
ord-5befff355db345938128d5a756581d78
Source dataset
uspto-grants-2001_08
Patent number
US06277872B1

Reaction notes

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