Hydrogen Bromide → Itraconazole Hydroxy Isopropyltriazolone Impurity

HRID 2073169Notes

Reaction equation

HRID 2073169 reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH:25]=[N:24][N:23]([CH:26]([CH3:28])[CH3:27])[C:22]4=[O:29])=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.Br>O>[OH:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:10][CH2:11][N:12]([C:15]3[CH:16]=[CH:17][C:18]([N:21]4[CH:25]=[N:24][N:23]([CH:26]([CH3:27])[CH3:28])[C:22]4=[O:29])=[CH:19][CH:20]=3)[CH2:13][CH2:14]2)=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 148553502,4-dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylethyl)-3H-1,2,4-triazol-3-one

Product 1

HCID 14855351Itraconazole Hydroxy Isopropyltriazolone ImpurityYield 86%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 4.7 parts of 2,4-dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylethyl)-3H-1,2,4-triazol-3-one and 75 parts of a hydrobromic acid solution 48% in water was stirred and refluxed for 3 hours. The reaction mixture was evaporated and the residue was dissolved in a mixture of methanol and water. The whole was neutralized with a sodium hydrogen carbonate solution and the product was extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was triturated in 2-propanol, yielding 3.9 parts (86%) of 2,4-dihydro-4-[4-[4-(4-hydroxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylethyl)-3H-1,2,4-triazol-3-one, mp. 208.4° C. (intermediate 10).

Workup

  1. temperaturerefluxed for 3 hours
  2. customThe reaction mixture was evaporated
  3. dissolutionthe residue was dissolved in a mixture of methanol and water
  4. extractionthe product was extracted with trichloromethane
  5. customThe extract was dried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was triturated in 2-propanol

Sources & evidence

ORD record
ord-759cd2de2bdc4c5b80b3c43d94bb2975
Source dataset
uspto-grants-1990_04
Patent number
US04916134

Reaction notes

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