Dichloromethane → 1-(2-Phenylpyrid-5-ylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt

HRID 363186Notes

Reaction equation

HRID 363186 reaction equation
[C:1]1([C:7]2[CH:12]=[CH:11][C:10]([CH2:13]O)=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(C(C)C)CC)(C)C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C([N:58]1[CH:62]=[C:61]([CH2:63][C:64]2[CH:69]=[CH:68][C:67]([C:70]#[N:71])=[CH:66][CH:65]=2)[N:60]=[CH:59]1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cl:72]CCl>>[ClH:72].[C:1]1([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][N:60]3[C:61]([CH2:63][C:64]4[CH:69]=[CH:68][C:67]([C:70]#[N:71])=[CH:66][CH:65]=4)=[CH:62][N:58]=[CH:59]3)=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 5

HCID 6344Dichloromethane2×HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 158375331-Trityl-4-(4-cyanobenzyl)imidazoleHCID 22254216(6-Phenylpyridin-3-yl)methanol

Product 1

HCID 703425471-(2-Phenylpyrid-5-ylmethyl)-5-(4-cyanobenzyl) imidazole hydrochloride salt

Conditions

Temperature
-78 °C

Procedure

To a solution of 2-phenyl-5-hydroxymethylpyridine (264 mg, 1.43 mmol) and diisopropylethylamine (0.522 mL, 3.00 mmol) in dichloromethane (10 mL) at -78° C. was added trifluoromethanesulfonic anhydride (0.252 mL, 1.50 mmol) and the mixture stirred at -78° C. for 15 minutes. To this mixture was added a solution of 1-trityl-4-(4-cyanobenzyl)imidazole (608 mg, 1.43 mmol) in dichloromethane (9 mL). The mixture was allowed to warm to ambient temperature and stirred for 16 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. NaHCO3 solution. The organic layer was dried, (Na2SO4) and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, 0-5% NH4OH 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. FAB MS 351 (MH+)

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred for 16 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. NaHCO3 solution
  9. customThe organic layer was dried
  10. custom(Na2SO4) and the solvent evaporated in vacuo
  11. customThe residue was chromatographed (Silica gel, 0-5% NH4OH in CH2Cl2)
  12. customEvaporation of the solvent in vacuo

Sources & evidence

ORD record
ord-38beba51444f43d495461c33bfcfb053
Source dataset
uspto-grants-1999_02
Patent number
US05872136

Reaction notes

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