Triethylamine → 2-acetyl-5-bromo-N-methyl-6-(methylsulfonamido)benzofuran-3-carboxamide

HRID 595603Notes

Reaction equation

HRID 595603 reaction equation
[C:1]([C:4]1[O:5][C:6]2[CH:16]=[C:15]([NH2:17])[C:14]([Br:18])=[CH:13][C:7]=2[C:8]=1[C:9]([NH:11][CH3:12])=[O:10])(=[O:3])[CH3:2].C(N(CC)CC)C.[CH3:26][S:27](Cl)(=[O:29])=[O:28].[Li+].[OH-].O>C1COCC1.O>[C:1]([C:4]1[O:5][C:6]2[CH:16]=[C:15]([NH:17][S:27]([CH3:26])(=[O:29])=[O:28])[C:14]([Br:18])=[CH:13][C:7]=2[C:8]=1[C:9]([NH:11][CH3:12])=[O:10])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 168937Lithium hydroxide, monohydrateHCID 903324142-acetyl-6-amino-5-bromo-N-methylbenzofuran-3-carboxamide

Product 1

HCID 903324982-acetyl-5-bromo-N-methyl-6-(methylsulfonamido)benzofuran-3-carboxamideYield 44.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 2-acetyl-6-amino-5-bromo-N-methylbenzofuran-3-carboxamide (500 mg, 1.61 mmol) and triethylamine (650 mg, 6.43 mmol) in THF (20 mL) was added MsCl (406 mg, 3.54 mmol) dropwise at 0° C. under N2. The mixture was stirred at room temperature for 1 hour. The mixture was quenched with H2O and extracted with EtOAc, and then the combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo to give the crude product. The crude product was dissolved in THF (20 mL) and then a solution of LiOH/H2O (200 mg/6 mL) was added. The mixture was stirred at room temperature for 1 hour, then water was added to the mixture and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo to give the crude product. The crude product was purified by column chromatography to give compound 2-acetyl-5-bromo-N-methyl-6-(methylsulfonamido)benzofuran-3-carboxamide (280 mg, yield: 44.8%). 1H-NMR (CDCl3, 400 MHz) δ 9.83 (s, 1H), 8.97 (s, 1H).7.91 (s, 1H), 7.07 (s, 1H), 3.06 (s, 3H), 3.02 (d, J=4.8 Hz, 3H), 2.77 (s, 3H). MS (M+H)+: 389/391.

Workup

  1. customThe mixture was quenched with H2O
  2. extractionextracted with EtOAc
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customto give the crude product
  7. stirringThe mixture was stirred at room temperature for 1 hour
  8. extractionextracted with EtOAc
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated in vacuo
  12. customto give the crude product
  13. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-6010deda5e3241588913396ed9ff2948
Source dataset
uspto-grants-2016_01
Patent number
US09242998B2

Reaction notes

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