Tetrabutylammonium Fluoride Trihydrate → 7-Ethynyl-2-(4-isopropylsulfonylphenyl)-5H-pyrrolo[2,3-b]pyrazine

HRID 467498Notes

Reaction equation

HRID 467498 reaction equation
[CH:1]([S:4]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]3[C:21]([C:22]#[C:23][Si](C)(C)C)=[CH:20][N:19](S(C4C=CC(C)=CC=4)(=O)=O)[C:16]3=[N:17][CH:18]=2)=[CH:9][CH:8]=1)(=[O:6])=[O:5])([CH3:3])[CH3:2].O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[C:22]([C:21]1[C:15]2[C:16](=[N:17][CH:18]=[C:13]([C:10]3[CH:9]=[CH:8][C:7]([S:4]([CH:1]([CH3:3])[CH3:2])(=[O:6])=[O:5])=[CH:12][CH:11]=3)[N:14]=2)[NH:19][CH:20]=1)#[CH:23]

Participants

4

Reactant 2

HCID 11726816Tetrabutylammonium Fluoride Trihydrate2×HCID 66764082HCID 66764082, compound

Product 1

HCID 866624437-Ethynyl-2-(4-isopropylsulfonylphenyl)-5H-pyrrolo[2,3-b]pyrazineYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-[2-(4-Isopropylsulfonylphenyl)-5-(p-tolylsulfonyl)pyrrolo[2,3-b]pyrazin-7-yl]ethynyl-trimethyl-silane (248 mg, 0.4495 mmol) in THF (5 mL) was treated with 1M tetrabutylammonium fluoride trihydrate (674.3 μL, 0.6743 mmol) and the reaction mixture allowed to stir at ambient temperature for 16 hours. A further portion of 1M tetrabutylammonium fluoride trihydrate (449.5 μL, 0.4495 mmol) was added and the reaction mixture warmed to 40° C. for 6 hours. The reaction was cooled to ambient temperature and added dropwise to a mixture of EtOAc/ice water and the layers separated. The organic layer was washed with 2M NaOH (×2), brine (×1), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column silica gel chromatography eluting with 15-20% EtOAc/DCM to give the sub-title compound as colourless crystals (89 mg, 61% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.20 (d, 6H), 3.40-3.50 (m, 1H), 4.20 (s, 1H), 8.00 (d, 2H), 8.33 (s, 1H), 8.44 (d, 2H), 9.06 (s, 1H) and 12.70 (s, 1H) ppm; MS (ES+) 326.0.

Workup

  1. temperaturethe reaction mixture warmed to 40° C. for 6 hours
  2. temperatureThe reaction was cooled to ambient temperature
  3. customthe layers separated
  4. washThe organic layer was washed with 2M NaOH (×2), brine (×1)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column silica gel chromatography
  9. washeluting with 15-20% EtOAc/DCM

Sources & evidence

ORD record
ord-6284ad8b79cf43b3a2f9d1701939624c
Source dataset
uspto-grants-2014_01
Patent number
US08623869B2

Reaction notes

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