Hydrochloric Acid → (2RS,5SR)-3-[5-(4-Fluoro-phenyl)-1-(toluene-4-sulfonyl)-pyrrolidin-2-yl]-1-methyl-1H-[1,2,4]triazole

HRID 890268Notes

Reaction equation

HRID 890268 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[N:13]([S:14]([C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=3)(=[O:16])=[O:15])[CH:12]([C:24]#[N:25])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[CH3:26][NH:27]N.[CH2:29]([N:31](CC)CC)C>CCO>[F:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]2[N:13]([S:14]([C:17]3[CH:18]=[CH:19][C:20]([CH3:23])=[CH:21][CH:22]=3)(=[O:16])=[O:15])[CH:12]([C:24]3[N:31]=[CH:29][N:27]([CH3:26])[N:25]=3)[CH2:11][CH2:10]2)=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6061MethylhydrazineHCID 8471TriethylamineHCID 22250432(2RS,5SR)-5-(4-Fluoro-phenyl)-1-(toluene-4-sulfonyl)-pyrrolidine-2-carbonitrile

Product 1

HCID 22250506(2RS,5SR)-3-[5-(4-Fluoro-phenyl)-1-(toluene-4-sulfonyl)-pyrrolidin-2-yl]-1-methyl-1H-[1,2,4]triazoleYield 64%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a freshly prepared solution of hydrochloric acid in EtOH (10 ml) was added at 0° C. (2RS,5SR)-5-(4-fluoro-phenyl)-1-(toluene-4-sulfonyl)-pyrrolidine-2-carbonitrile (0.50 g, 1.45 mmol), the reaction mixture was stirred at room temperature for 1.5 h and evaporated. The light brown solid (0.65 g) was dissolved in EtOH (10 ml), methylhydrazine (86.9 mg, 1.89 mmol) and triethylamine (0.51 ml, 3.63 mmol) were added and the mixture was stirred at room temperature for 2 h. The reaction mixture was evaporated, subsequently dissolved in formic acid (10 ml), stirred at room temperature for 0.5 h and heated under reflux conditions for 1.5 h. Evaporation, aqueous work-up, column chromatography on silica gel (ethyl acetate) and crystallization from ethyl acetate/hexane yielded the title compound (0.37 g, yield 64%) as a white solid, m.p. 160° C. and MS: m/e=400 (M+).

Workup

  1. customevaporated
  2. dissolutionThe light brown solid (0.65 g) was dissolved in EtOH (10 ml)
  3. stirringthe mixture was stirred at room temperature for 2 h
  4. customThe reaction mixture was evaporated
  5. dissolutionsubsequently dissolved in formic acid (10 ml)
  6. stirringstirred at room temperature for 0.5 h
  7. temperatureheated under reflux conditions for 1.5 h
  8. customEvaporation, aqueous work-up, column chromatography
  9. customon silica gel (ethyl acetate) and crystallization from ethyl acetate/hexane

Sources & evidence

ORD record
ord-204f50b6c9e54e979f4885218a961161
Source dataset
uspto-grants-2006_02
Patent number
US06995182B2

Reaction notes

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