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

HRID 85026Notes

Reaction equation

HRID 85026 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 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of N-(5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-yl)acetamide [Intermediate AR] (2.6 g, 8.4 mmol) and tetrabutylammonium fluoride [1 M in THF] (18 mL, 18 mmol) in anhydrous THF (26 mL) was heated at 75° C. for 20 h, after which it was partitioned between EtOAc and H2O. The organic layer was washed with brine, dried over Na2SO4, and evaporated in vacuo to yield a residue that was purified via silica gel chromatography eluting with 30% EtOAc in hexanes to give the title compound as a tan solid (0.69 g, 42%). 1H NMR (CDCl3, 300 MHz): δ 8.88 (bs, 1H), 8.34 (s, 1H), 7.62 (t, J=3.3 Hz, 1H), 6.71 (dd, J=3.6 Hz, 3.9 Hz, 1H). HPLC retention time: 1.73 minutes. MS ESI (m/z): 198.2, 200.2 (M+H)+, calc. 197.

Workup

  1. customafter which it was partitioned between EtOAc and H2O
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. customevaporated in vacuo
  5. customto yield a residue that
  6. customwas purified via silica gel chromatography
  7. washeluting with 30% EtOAc in hexanes

Sources & evidence

ORD record
ord-fb993057e7244fe8a1fa5cd40c9368c5
Source dataset
uspto-grants-2014_09
Patent number
US08846909B2

Reaction notes

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