Dichloromethane → 1-(4-[Thien-3-yl]phenylmethyl)-5-(4-cyanobenzyl)imidazole hydrochloride salt

HRID 1585865Notes

Reaction equation

HRID 1585865 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:13]=[CH:12][C:9]([CH2:10]O)=[CH:8][CH:7]=2)=[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:57]1[CH:61]=[C:60]([CH2:62][C:63]2[CH:68]=[CH:67][C:66]([C:69]#[N:70])=[CH:65][CH:64]=2)[N:59]=[CH:58]1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cl:71]CCl>>[ClH:71].[S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:13]=[CH:12][C:9]([CH2:10][N:59]3[C:60]([CH2:62][C:63]4[CH:68]=[CH:67][C:66]([C:69]#[N:70])=[CH:65][CH:64]=4)=[CH:61][N:57]=[CH:58]3)=[CH:8][CH:7]=2)=[CH:2]1

Participants

6

Reactant 5

HCID 6344Dichloromethane2×HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 15186379(4-(Thiophen-3-yl)phenyl)methanolHCID 158375331-Trityl-4-(4-cyanobenzyl)imidazole

Product 1

HCID 212194501-(4-[Thien-3-yl]phenylmethyl)-5-(4-cyanobenzyl)imidazole hydrochloride salt

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-thien-3-yl-benzyl alcohol (253 mg, 1.33 mmol) and diisopropylethylamine (0.464 mL, 2.66 mmol) in dichloromethane (7 mL) at -78° C. was added trifluoromethanesulfonic anhydride (0.224 mL, 1.33 mmol) and the mixture stirred at -78° C. for 1 hour. To this mixture was added a solution of 1-trityl-4-(4-cyanobenzyl)-imidazole (566 mg , 1.33 mmol) in dichloromethane (5 mL). The mixture was allowed to warm to ambient temperature and stirred for 2 hours. The solvent was evaporated in vacuo. The residue was dissolved in methanol (50 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, 2% MeOH in CH2Cl2) and 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 2 hours
  3. customThe solvent was evaporated in vacuo
  4. dissolutionThe residue was dissolved in methanol (50 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, 2% MeOH in CH2Cl2)
  12. customEvaporation of the solvent in vacuo

Sources & evidence

ORD record
ord-0e0292454d5144c288a0219fc254e915
Source dataset
uspto-grants-1999_08
Patent number
US05939557

Reaction notes

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