Tetrabutylammonium Fluoride → 2-bromo-5H-pyrrolo[2,3-b]pyrazine

HRID 1865682Notes

Reaction equation

HRID 1865682 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([C:12]#[C:13][Si](C)(C)C)[C:5]([NH:8]C(=O)C)=[N:6][CH:7]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[Br:1][C:2]1[N:3]=[C:4]2[CH:12]=[CH:13][NH:8][C:5]2=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 59836029N-(5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-yl)acetamide

Product 1

HCID 250673082-bromo-5H-pyrrolo[2,3-b]pyrazineYield 43.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of N-(5-Bromo-3-trimethylsilanylethynyl-pyrazin-2-yl)-acetamide (474 mg, 1.52 mmol) in THF (4 ml) was added dropwise a 1 M solution of tetra-n-butyl ammonium fluoride in THF (3.3 ml, 3.3 mmol). After stirring at reflux for 15 hours, the reaction mixture was concentrated in vacuum and water added. The aqueous layer was extracted three times with dichloromethane and the combined extracts were directly adsorbed on silica gel. Purification by silica gel chromatography with a gradient of ethyl acetate/hexanes afforded the title compound (130 mg, 43% yield) as a yellow solid. 1H-NMR (500 MHz, d6-DMSO) (12.38 (s br, 1H), 8.38 (s, 1H), 7.95 (d, 3.5 Hz, 1H), 6.61 (d, 3.5 Hz, 1H). MS: m/z 197.9/199.9 [MH+].

Workup

  1. temperatureat reflux for 15 hours
  2. concentrationthe reaction mixture was concentrated in vacuum and water
  3. additionadded
  4. extractionThe aqueous layer was extracted three times with dichloromethane
  5. customPurification by silica gel chromatography with a gradient of ethyl acetate/hexanes

Sources & evidence

ORD record
ord-8fb92a002b1d4eb59f69d99420762369
Source dataset
uspto-grants-2009_12
Patent number
US07626021B2

Reaction notes

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