Tetrabutylammonium Fluoride → 4-(4-isobutylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide

HRID 361424Notes

Reaction equation

HRID 361424 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH2:19]([C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][N:32]=[CH:31][C:30]=2[S:35]([N:38]([C:47]2[C:52]([O:53][CH3:54])=[N:51][C:50]([CH3:55])=[CH:49][N:48]=2)COCC[Si](C)(C)C)(=[O:37])=[O:36])=[CH:25][CH:24]=1)[CH:20]([CH3:22])[CH3:21]>C1COCC1.O>[CH2:19]([C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][N:32]=[CH:31][C:30]=2[S:35]([NH:38][C:47]2[C:52]([O:53][CH3:54])=[N:51][C:50]([CH3:55])=[CH:49][N:48]=2)(=[O:37])=[O:36])=[CH:25][CH:24]=1)[CH:20]([CH3:22])[CH3:21]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium Fluoride2×HCID 211862384-(4-isobutylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)-N-[2-(trimethylsilyl)ethoxymethyl]pyridine-3-sulphonamide

Product 1

HCID 211862424-(4-isobutylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamideYield 9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Tetrabutylammonium fluoride (0.45 ml of a 1.0M solution in THF) was added to a solution of 4-(4-isobutylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)-N-[2-(trimethylsilyl)ethoxymethyl]pyridine-3-sulphonamide (0.205 g) in dry THF (2 ml) and the solution was heated under reflux for 40 minutes. More tetrabutylammonium fluoride solution (0.95 ml) was added and heating was continued for 2 hours. The reaction mixture was diluted with water (15 ml) and extracted with ether (2×30 ml). The organic extracts were washed with water and saturated sodium chloride solution and then dried (MgSO4). Volatile material was removed by evaporation and the residue was purified by gradient elution with 40-50% ethyl acetate/hexane through a silica gel Mega Bond Elut column followed by recrystallisation from ethyl acetate/hexane to give 4-(4-isobutylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (0.014 g), m.p. 232°-233° C.; 1H NMR (d6 -DMSO): 0.9 (d, 6 H), 1.8 (br m, 1 H), 2.1-2.5 (br m, 5 H), 3.8 (s, 3 H), 7.1-7.3 (m, 4 H), 7.35 (d, 1 H), 7.5 (s, 1 H), 8.75 (d, 1 H), 9.1 (s, 1 H), 10.4 (s, 1 H); mass spectrum (+ve ESP): 413 (M+H)+.

Workup

  1. temperaturethe solution was heated
  2. temperatureunder reflux for 40 minutes
  3. temperatureheating
  4. extractionextracted with ether (2×30 ml)
  5. washThe organic extracts were washed with water and saturated sodium chloride solution
  6. dry with materialdried (MgSO4)
  7. customVolatile material was removed by evaporation
  8. customthe residue was purified by gradient elution with 40-50% ethyl acetate/hexane through a silica gel Mega Bond Elut column
  9. customfollowed by recrystallisation from ethyl acetate/hexane

Sources & evidence

ORD record
ord-d92cbe5fa1454bb2a3d263cf2e16546a
Source dataset
uspto-grants-1999_02
Patent number
US05866568

Reaction notes

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