Triethylamine → 5-Bromoisoquinoline-1-carbonitrile

HRID 272771Notes

Reaction equation

HRID 272771 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N+:6]([O-])=[CH:7]2.C[CH2:14][N:15](CC)CC.[Si](C#N)(C)(C)C>CC#N>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[C:7]2[C:14]#[N:15]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 82115Trimethylsilyl cyanide2×HCID 22665708Isoquinoline, 5-bromo-, 2-oxide

Product 1

HCID 692192105-Bromoisoquinoline-1-carbonitrileYield 90%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of Example 795A (0.30 g, 1.34 mmol), Et3N (0.270 g, 2.68 mmol) and TMSCN (0.18 g, 2 mmol) in CH3CN (10 mL) was heated under reflux overnight. More Et3N (0.27 g, 2.68 mmol) and TMSCN (0.18 g, 2 mmol) were added, and the reaction mixture was heated under reflux for another 16 hours. The reaction mixture was partitioned between water and EtOAc. The aqueous layer was extracted with additional EtOAc. The combined organic layers were washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with 4:1 Hexanes/EtOAc to give 0.28 g of the title compound (90%). MS (APCI) m/e 234 (M+H)+, 1H NMR (500 MHz, DMSO-d6): □ 8.85 (d, J=5.62 Hz, 1H), 8.35 (d, J=7.49 Hz, 1H), 8.29-8.33 (m, 2H), 7.85 (m, 1H).

Workup

  1. temperatureunder reflux overnight
  2. temperaturethe reaction mixture was heated
  3. temperatureunder reflux for another 16 hours
  4. customThe reaction mixture was partitioned between water and EtOAc
  5. extractionThe aqueous layer was extracted with additional EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography
  10. washeluting with 4:1 Hexanes/EtOAc

Sources & evidence

ORD record
ord-df3035f8586a4cc18360392ac51e8677
Source dataset
uspto-grants-2008_11
Patent number
US07456169B2

Reaction notes

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