Hydrochloric Acid → 5-(1-benzyl-1H-imidazol-2-yl)-2-bromo-4-(2,4-dichlorophenyl)thiophene-3-carbonitrile

HRID 2402454Notes

Reaction equation

HRID 2402454 reaction equation
[CH2:1]([NH:8][C:9]([C:11]1[S:12][C:13]([Br:26])=[C:14]([C:24]#[N:25])[C:15]=1[C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=1[Cl:23])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)(Cl)Cl.Cl.O1CCOCC1.CO[CH:42](OC)[CH2:43][NH2:44]>C(Cl)Cl>[CH2:1]([N:8]1[CH:42]=[CH:43][N:44]=[C:9]1[C:11]1[S:12][C:13]([Br:26])=[C:14]([C:24]#[N:25])[C:15]=1[C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=1[Cl:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 313Hydrochloric Acid2×HCID 24819Phosphorus pentachlorideHCID 312751,4-Dioxane2×HCID 89728Aminoacetaldehyde dimethyl acetalHCID 66854726N-benzyl-5-bromo-4-cyano-3-(2,4-dichlorophenyl)thiophene-2-carboxamide

Product 1

HCID 668562415-(1-benzyl-1H-imidazol-2-yl)-2-bromo-4-(2,4-dichlorophenyl)thiophene-3-carbonitrileYield 58.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

N-benzyl-5-bromo-4-cyano-3-(2,4-dichlorophenyl)thiophene-2-carboxamide (0.180 g, 0.386 mmol) was dissolved in DCM (2 mL) and phosphorus pentachloride (0.0884 g, 0.425 mmol) and 4.00 M of Hydrochloric acid in 1,4-dioxane (0.050 mL, 0.20 mmol) were added. The mixture was heated in a sealed vial at 60° C. for 2 hours. After cooling down to room temperature, aminoacetaldehyde dimethyl acetal (0.252 mL, 2.32 mmol) was slowly added. The mixture was heated at 60° C. for additional 1 hour. After cooling to room temperature, 4.00 M of Hydrochloric acid in 1,4-dioxane (1.0 mL, 4.0 mmol) was added and the mixture was heated at 60° C. for 2 hours and at room temperature overnight. Solvent was concentrated and the residue was diluted with EA, washed with saturated NaHCO3, brine, dried with Na2SO4, filtered and evaporated. The residue was purified using ISCO chromatography on silica gel, elution with 10-25% EA in hexanes to give the product (0.110 g, 58%). LCMS: (FA) ES+, 488, 490, 492. 1H NMR (300 MHz, d1-chloroform) δ: 7.28 (d, J=2.07 Hz, 1H), 7.26-7.15 (m, 5H), 7.11-7.08 (d, J=8.29 Hz, 1H), 6.85 (s, 1H), 6.73-6.70 (dd, J=6.97 Hz, 1.66 Hz, 2H). 4.85-4.70 (m, 2H).

Workup

  1. temperatureAfter cooling down to room temperature
  2. temperatureThe mixture was heated at 60° C. for additional 1 hour
  3. temperatureAfter cooling to room temperature
  4. temperaturethe mixture was heated at 60° C. for 2 hours and at room temperature overnight
  5. concentrationSolvent was concentrated
  6. additionthe residue was diluted with EA
  7. washwashed with saturated NaHCO3, brine
  8. dry with materialdried with Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified
  12. washon silica gel, elution with 10-25% EA in hexanes

Sources & evidence

ORD record
ord-a0fb338c680e4ea3b463dacda581c677
Source dataset
uspto-grants-2014_08
Patent number
US08796314B2

Reaction notes

Loading…