Triethylamine → HCID 54597253, compound

HRID 522532Notes

Reaction equation

HRID 522532 reaction equation
CCN(CC)CC.[C:8]([C:10]1[CH:15]=[N:14][CH:13]=[C:12]([C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH:25]([CH3:27])[CH3:26])(=[O:24])=[O:23])=[CH:18][CH:17]=2)[N:11]=1)#[CH:9].[OH:28][N:29]=[C:30](Cl)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>CN(C=O)C.CCOC(C)=O.O>[CH:25]([S:22]([C:19]1[CH:20]=[CH:21][C:16]([C:12]2[N:11]=[C:10]([C:8]3[O:28][N:29]=[C:30]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[CH:9]=3)[CH:15]=[N:14][CH:13]=2)=[CH:17][CH:18]=1)(=[O:24])=[O:23])([CH3:27])[CH3:26]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 2756315N-hydroxybenzenecarboximidoyl chlorideHCID 86665149HCID 86665149, compound

Product 1

HCID 54597253HCID 54597253, compoundYield 33%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Et3N (27.56 mg, 37.96 μL, 0.2724 mmol) was added to a stirred solution of 2-ethynyl-6-(4-isopropylsulfonylphenyl)pyrazine (65 mg, 0.2270 mmol) and N-hydroxybenzimidoyl chloride (35.32 mg, 0.2270 mmol) in DMF (2 mL) and the reaction was stirred at ambient temperature for 45 minutes then heated to 65° C. for 1 hour. The mixture was cooled to ambient temperature and diluted with EtOAc and water and the layers separated. The aqueous layer was extracted with EtOAc (×2) and the combined organic extracts washed with water (×3), brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion™, 12 g column, eluting with 0 to 40% EtOAc/Petroleum Ether) and the relevant fractions concentrated in vacuo. The residue was triturated from methanol and the precipitate isolated by filtration to give the title product as a cream solid (30 mg, 33% Yield). 1H NMR (400.0 MHz, DMSO) H NMR (400.0 MHz, DMSO) d 9.53 (s, 1H), 9.32 (s, 1H), 8.58 (d, 2H), 8.09-8.07 (m, 3H), 8.04-8.02 (m, 2H), 7.61-7.57 (m, 3H), 3.55 (sept, 1H) and 1.21 (d, 6H) ppm; MS (ES+) 406.1; LCMS Retention time 1.72 min.

Workup

  1. temperaturethen heated to 65° C. for 1 hour
  2. temperatureThe mixture was cooled to ambient temperature
  3. customthe layers separated
  4. extractionThe aqueous layer was extracted with EtOAc (×2)
  5. washthe combined organic extracts washed with water (×3), brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (ISCO Companion™, 12 g column, eluting with 0 to 40% EtOAc/Petroleum Ether)
  9. concentrationthe relevant fractions concentrated in vacuo
  10. customThe residue was triturated from methanol
  11. customthe precipitate isolated by filtration

Sources & evidence

ORD record
ord-730d963c00ef40788df4629e65b04d63
Source dataset
uspto-grants-2016_05
Patent number
US09334244B2

Reaction notes

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