Dichloromethane → 1-(2-(3-Trifluoromethoxyphenyl)-pyrid-5-ylmethyl)-5-(4-cyanobenzyl)imidazole hvdrochloride salt

HRID 363192Notes

Reaction equation

HRID 363192 reaction equation
[F:1][C:2]([F:19])([F:18])[O:3][C:4]1[CH:5]=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16]O)=[CH:12][N:11]=2)[CH:7]=[CH:8][CH:9]=1.C(N(C(C)C)CC)(C)C.C([N:48]1[CH:52]=[C:51]([CH2:53][C:54]2[CH:59]=[CH:58][C:57]([C:60]#[N:61])=[CH:56][CH:55]=2)[N:50]=[CH:49]1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[Cl:77]CCl>>[ClH:77].[F:1][C:2]([F:19])([F:18])[O:3][C:4]1[CH:5]=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:50]3[C:51]([CH2:53][C:54]4[CH:59]=[CH:58][C:57]([C:60]#[N:61])=[CH:56][CH:55]=4)=[CH:52][N:48]=[CH:49]3)=[CH:12][N:11]=2)[CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 158375331-Trityl-4-(4-cyanobenzyl)imidazoleHCID 24729919(6-(3-(Trifluoromethoxy)phenyl)pyridin-3-yl)methanol

Product 1

HCID 675623221-(2-(3-Trifluoromethoxyphenyl)-pyrid-5-ylmethyl)-5-(4-cyanobenzyl)imidazole hvdrochloride salt

Conditions

Temperature
-78 °C

Procedure

To a solution of 2-(3-trifluoromethoxyphenyl)-5-hydroxymethylpyridine (66 mg, 0.25 mmol), diisopropylethylamine (0.085 mL, 0.49 mmol), and 1-trityl-4-(4-cyanobenzyl)imidazole (105 mg, 0.25 mmol) in dichloromethane (1.4 mL) at -78° C. was added trifluoromethanesulfonic anhydride (0.041 mL, 0.25 mmol) and the mixture stirred at -78° C. for 1 hour. The reaction was allowed to warm to ambient temperature and stirred for 4 hours. The solvent was evaporated in vacuo. The residue was dissolved in methanol (15 mL), heated at reflux for 1 hour, and the solvent evaporated in vacuo. The residue was partitioned between dichloromethane and sat. aq. Na2CO3 solution. The organic layer was dried, (Na2SO4) and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, 3% MeOH in CH2Cl2). The amine was converted to the HCl salt by treatment with 1.0M HCl in aqueous acetonitrile. Evaporation of the solvent in vacuo afforded the title compound as a white solid.

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred for 4 hours
  3. customThe solvent was evaporated in vacuo
  4. dissolutionThe residue was dissolved in methanol (15 mL)
  5. temperatureheated
  6. temperatureat reflux for 1 hour
  7. customthe solvent evaporated in vacuo
  8. customThe residue was partitioned between dichloromethane and sat. aq. Na2CO3 solution
  9. customThe organic layer was dried
  10. custom(Na2SO4) and the solvent evaporated in vacuo
  11. customThe residue was chromatographed (Silica gel, 3% MeOH in CH2Cl2)
  12. customEvaporation of the solvent in vacuo

Sources & evidence

ORD record
ord-5286d76e0ae2449d97eea7edc5ca9e92
Source dataset
uspto-grants-1999_02
Patent number
US05872136

Reaction notes

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