Sodium Bicarbonate → N-(5-Bromo-2-methoxy-3-pyridinyl)-4-hydroxy-3-methylbenzenesulfonamide

HRID 1052497Notes

Reaction equation

HRID 1052497 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH2:10])[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[OH:21][C:22]1[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][C:23]=1[CH3:32].C(=O)(O)[O-].[Na+]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:10][S:28]([C:25]2[CH:26]=[CH:27][C:22]([OH:21])=[C:23]([CH3:32])[CH:24]=2)(=[O:30])=[O:29])[C:5]([O:8][CH3:9])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 447548695-Bromo-2-methoxypyridin-3-amineHCID 552806724-Hydroxy-3-methylbenzene-1-sulfonyl chloride

Product 1

HCID 90103380N-(5-Bromo-2-methoxy-3-pyridinyl)-4-hydroxy-3-methylbenzenesulfonamideYield 12%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

5-Bromo-2-methoxypyridin-3-amine (1.08 g, 5.32 mmol) was dissolved in THF (2.5 ml) and cooled with an ice bath. A solution of sodium bis(trimethylsilyl)amide (1 M in THF, 8 ml, 8 mmol) was added dropwise. Ten minutes later, 4-hydroxy-3-methylbenzene-1-sulfonyl chloride (1.65 g, 5.91 mmol, prepared according to JP 47015818 B4 19720511) in THF (3 ml) was added and the reaction mixture was allowed to reach room temperature. After stirring for 1 h, a saturated solution of sodium bicarbonate was added dropwise and the reaction mixture was extracted with dichloromethane (×3). The organic phase was dried over magnesium sulphate, filtered and the solvent evaporated under reduced pressure. The resulting residue was purified by reverse phase chromatography using SP1® Purification System (C-18 silica from Waters®, water/1:1 acetonitrile-methanol as eluents [0.1% v/v formic acid buffered] 0% to 100%) to give 230 mg (12% yield) of the title compound. Purity 100%.

Workup

  1. temperaturecooled with an ice bath
  2. customto reach room temperature
  3. extractionthe reaction mixture was extracted with dichloromethane (×3)
  4. dry with materialThe organic phase was dried over magnesium sulphate
  5. filtrationfiltered
  6. customthe solvent evaporated under reduced pressure
  7. customThe resulting residue was purified by reverse phase chromatography
  8. customSP1® Purification System (C-18 silica from Waters®, water/1:1 acetonitrile-methanol as eluents [0.1% v/v formic acid

Sources & evidence

ORD record
ord-672eabffd1a449a0b3a4700721c90127
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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