4-Fluorobenzenesulfonyl chloride → N-(5-bromo-3-methoxypyridin-2-yl)-4-fluorobenzenesulfonamide

HRID 594121Notes

Reaction equation

HRID 594121 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH3:10])[C:5]([NH2:8])=[N:6][CH:7]=1.[F:11][C:12]1[CH:17]=[CH:16][C:15]([S:18](Cl)(=[O:20])=[O:19])=[CH:14][CH:13]=1>N1C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH3:10])[C:5]([NH:8][S:18]([C:15]2[CH:16]=[CH:17][C:12]([F:11])=[CH:13][CH:14]=2)(=[O:20])=[O:19])=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 95884-Fluorobenzenesulfonyl chlorideHCID 222714075-Bromo-3-methoxypyridin-2-amine

Product 1

HCID 89876109N-(5-bromo-3-methoxypyridin-2-yl)-4-fluorobenzenesulfonamideYield 74.7%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Conditions

Temperature
20 °C

Procedure

To a solution of 5-bromo-3-methoxypyridin-2-amine (100 mg, 0.493 mmol) in pyridine (1 mL) stirred in air at room temperature was added a solution of 4-fluorobenzene-1-sulfonyl chloride (115 mg, 0.591 mmol) in pyridine (1 mL). The reaction mixture was stirred at 20° C. for 16 hours then the solvent was evaporated in vacuo to give the crude product. The crude was passed through an aminopropyl (NH2) solid phase extraction (SPE) cartridge eluting with methanol followed by 2M ammonia/methanol, then a sulphonic acid (SCX) SPE cartridge eluting with methanol followed by 2M ammonia/methanol. The appropriate fractions were combined and evaporated under a stream of nitrogen to give the crude product. Final purification by flash silica (Si) chromatography (0-100% ethyl acetate-cyclohexane+0-20% methanol gradient), gave the title product (133 mg) as an off-white solid. LCMS (2 min, formic) Rt 1.03 min, m/z (ES+) 361/363 (M+H).

Workup

  1. customthe solvent was evaporated in vacuo
  2. customto give the crude product
  3. extractionThe crude was passed through an aminopropyl (NH2) solid phase extraction (SPE) cartridge
  4. washeluting with methanol
  5. washa sulphonic acid (SCX) SPE cartridge eluting with methanol
  6. customevaporated under a stream of nitrogen
  7. customto give the crude product
  8. customFinal purification by flash silica (Si) chromatography (0-100% ethyl acetate-cyclohexane+0-20% methanol gradient)

Sources & evidence

ORD record
ord-75b6b796bad74d168e5b507834e505c4
Source dataset
uspto-grants-2016_01
Patent number
US09242972B2

Reaction notes

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