Water → HCID 178487396, compound

HRID 2410013Notes

Reaction equation

HRID 2410013 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH2:18][C:19]3[N:24]=[C:23](/[CH:25]=[CH:26]/[C:27]#[N:28])[CH:22]=[CH:21][CH:20]=3)=[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[NH:9]2)=[CH:5][CH:4]=1.C(O)(C)C.O.[N-:34]=[N+:35]=[N-:36].[Na+]>Cl.[Br-].[Zn+2].[Br-]>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH2:18][C:19]3[CH:20]=[CH:21][CH:22]=[C:23](/[CH:25]=[CH:26]/[C:27]4[NH:36][N:35]=[N:34][N:28]=4)[N:24]=3)=[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[NH:9]2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 962Water3×HCID 3776Isopropanol2×HCID 33557Sodium AzideHCID 86703316HCID 86703316, compound

Product 1

HCID 178487396HCID 178487396, compoundYield 34.5%

Reagents, catalysts & solvents 2

HCID 10421208Zinc bromideCatalystHCID 313Hydrochloric AcidSolvent

Procedure

To a mixture of (E)-3-[6-(6-methoxy-2-phenyl-1H-indol-3-ylmethyl)pyridin-2-yl]acrylonitrile (67 mg), isopropyl alcohol (1.5 mL) and water (0.5 mL) were added sodium azide (59.6 mg) and zinc bromide (51.6 mg), and the mixture was heated under reflux for 32 hours. Then isopropyl alcohol (1.5 mL) and water (0.5 mL) were added thereto, followed by heating under reflux for 62 hours. The reaction mixture was left to be cooled, diluted with 1 mol/L hydrochloric acid, and then stirred for 5 minutes. To the mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (25.8 mg). 1H-NMR (DMSO-d6) δ ppm: 3.77 (3H, s), 4.34 (2H, s), 6.65 (1H, dd, J=2.3, 8.5 Hz), 6.87 (1H, d, J=2.3 Hz), 7.16-7.23 (1H, m), 7.32-7.43 (2H, m), 7.46-7.54 (3H, m), 7.65-7.85 (5H, m), 11.16 (1H, s). ESI-MS (m/z): 409 (M+H)+

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 32 hours
  3. temperatureby heating
  4. temperatureunder reflux for 62 hours
  5. waitThe reaction mixture was left
  6. temperatureto be cooled
  7. extractionfollowed by extraction with ethyl acetate
  8. washThe organic layer was washed with water
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-72c3ee5f65994aada480e5818291c402
Source dataset
uspto-grants-2014_08
Patent number
US08815903B2

Reaction notes

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