Methylamine → 5-(Aminosulfonyl)-2-fluoro-N-methylbenzamide

HRID 398085Notes

Reaction equation

HRID 398085 reaction equation
[NH2:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([F:14])=[C:9]([CH:13]=1)[C:10](O)=[O:11])(=[O:4])=[O:3].[C:15](N1C=CN=C1)([N:17]1C=CN=C1)=O.CN>C1COCC1>[NH2:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([F:14])=[C:9]([CH:13]=1)[C:10]([NH:17][CH3:15])=[O:11])(=[O:4])=[O:3]

Participants

5

Reactant 3

HCID 6329MethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 24926842-Fluoro-5-sulfamoylbenzoic acid

Product 1

HCID 230018165-(Aminosulfonyl)-2-fluoro-N-methylbenzamideYield 81.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 5-(aminosulfonyl)-2-fluorobenzoic acid [prepared according to Chem. Pharm. Bull. 1995, 43, 582-7] (22.98 g, 105 mmol) in THF (500 mL) at room temperature under nitrogen was added carbonyldiimidazole (17 g, 105 mmol). After stirring for 2.25 h a solution of methylamine in THF (2M, 70 mL, 140 mmol) was added dropwise and the reaction was allowed to stir for 18 h. The crude reaction mixture was concentrated to a low volume and EtOAc (150 mL) was added to the resulting thick oil. This mixture was stirred and a granular precipitate formed which was collected by filtration. This crude product, contaminated with imidazole, was suspended in DCM (300 mL) and heated at reflux for 5 h. After cooling to room temperature the mixture was filtered to give the desired product (19.8 g, 81%) containing <2% w/w imidazole; 1H NMR δH (300 MHz, d4-MeOH) 2.97 (3H, s), 7.40 (1H, t), 8.05 (1H, m), 8.29 (1H, d); MS m/z (TS+) 250 (MNH4+).

Workup

  1. additionwas added dropwise
  2. customThe crude reaction mixture
  3. concentrationwas concentrated to a low volume and EtOAc (150 mL)
  4. additionwas added to the resulting thick oil
  5. stirringThis mixture was stirred
  6. customa granular precipitate formed which
  7. filtrationwas collected by filtration
  8. temperatureheated
  9. temperatureat reflux for 5 h
  10. filtrationwas filtered

Sources & evidence

ORD record
ord-8c60045031a64060bdcd35518791247e
Source dataset
uspto-grants-2003_08
Patent number
US06610747B2

Reaction notes

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