4-Fluorobenzenesulfonyl chloride → N-(5-chloro-3-methylpyridin-2-yl)-4-fluorobenzenesulfonamide

HRID 594115

Reaction equation

HRID 594115 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH3:9])[C:5]([NH2:8])=[N:6][CH:7]=1.[F:10][C:11]1[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1>N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([CH3:9])[C:5]([NH:8][S:17]([C:14]2[CH:15]=[CH:16][C:11]([F:10])=[CH:12][CH:13]=2)(=[O:19])=[O:18])=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 95884-Fluorobenzenesulfonyl chlorideHCID 3502322-Amino-5-chloro-3-methylpyridine

Product 1

HCID 89876053N-(5-chloro-3-methylpyridin-2-yl)-4-fluorobenzenesulfonamideYield 47.6%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Conditions

Temperature
20 °C

Procedure

To a solution of 5-chloro-3-methylpyridin-2-amine (500 mg, 3.51 mmol) in pyridine (7 mL) stirred in air at room temperature was added a solution of 4-fluorobenzene-1-sulfonyl chloride (819 mg, 4.21 mmol) in pyridine (7 mL). The reaction mixture was stirred at 20° C. for 16 hours then the solvent was evaporated in vacuo. 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. The crude was purified by flash silica (Si) chromatography (0-100% ethyl acetate-cyclohexane+0-20% methanol gradient). The appropriate fractions were combined and evaporated in vacuo to give the title compound (502 mg) as an off-white solid. LCMS (2 min, formic) Rt 1.02 min, m/z (ES+) 301 (M+H).

Workup

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

Sources & evidence

ORD record
ord-1b28b376a0944a7cb6660adc1d8ac78f
Source dataset
uspto-grants-2016_01
Patent number
US09242972B2

Linked notes

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