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

HRID 1357126Notes

Reaction equation

HRID 1357126 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), methyl-hydrazine (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-0f6fe079eac84c3ca910ebf1057c4513
Source dataset
uspto-grants-2003_07
Patent number
US06589978B2

Reaction notes

Loading…