1-(2-Amino-3,5-dimethylphenyl)ethan-1-one → N-(2-acetyl-4,6-dimethylphenyl)-3-(((4-chloro-3-methyl-5-isoxazolyl)amino)sulfonyl)-2-thiophenecarboxamide

HRID 1841409Notes

Reaction equation

HRID 1841409 reaction equation
[NH2:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([CH3:9])=[CH:4][C:3]=1[C:10](=[O:12])[CH3:11].[Cl:13][C:14]1[C:15]([CH3:34])=[N:16][O:17][C:18]=1[N:19](COC)[S:20]([C:23]1[CH:27]=[CH:26][S:25][C:24]=1[C:28](Cl)=[O:29])(=[O:22])=[O:21]>ClCCl>[C:10]([C:3]1[CH:4]=[C:5]([CH3:9])[CH:6]=[C:7]([CH3:8])[C:2]=1[NH:1][C:28]([C:24]1[S:25][CH:26]=[CH:27][C:23]=1[S:20]([NH:19][C:18]1[O:17][N:16]=[C:15]([CH3:34])[C:14]=1[Cl:13])(=[O:21])=[O:22])=[O:29])(=[O:12])[CH3:11]

Participants

4

Reactant 2

HCID 105831361-(2-Amino-3,5-dimethylphenyl)ethan-1-oneHCID 10738841HCID 10738841, compound

Product 1

HCID 9934302N-(2-acetyl-4,6-dimethylphenyl)-3-(((4-chloro-3-methyl-5-isoxazolyl)amino)sulfonyl)-2-thiophenecarboxamideYield 43.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2′-amino-3′,5′-dimethylacetophenone (1.9 g, 11.66 mmol) in dichloromethane (20 mL) at room temperature was added N-(4-chloro-3-methyl-5-isoxazolyl)-N-methoxymethyl-3-sulfamoyl-2-thiophenecarbonyl chloride (Example 51) (1 g, 2.86 mmol). The mixture was stirred for 10 h during which much yellow precipitate formed. The reaction was then concentrated and the residue was diluted with ethyl acetate (50 mL) and washed with 1 N HCl (50 mL). The organic layer was concentrated and the residue was dissolved in methanol (30 mL) followed by the addition of concentrated HCl (15 mL). The mixture was then heated under reflux for 2 h before it was cooled to room temperature, diluted with ethyl acetate (200 mL) and washed with water (2×200 mL). The organic layer was separated, dried (MgSO4), the solids filtered and the filtrate concentrated. The residue was then purified by reverse phase HPLC to give N-(2-acetyl-4,6-dimethylphenyl)-3-(((4-chloro-3-methyl-5-isoxazolyl)amino)sulfonyl)-2-thiophenecarboxamide (580 mg, 43%).

Workup

  1. customformed
  2. concentrationThe reaction was then concentrated
  3. additionthe residue was diluted with ethyl acetate (50 mL)
  4. washwashed with 1 N HCl (50 mL)
  5. concentrationThe organic layer was concentrated
  6. dissolutionthe residue was dissolved in methanol (30 mL)
  7. additionfollowed by the addition of concentrated HCl (15 mL)
  8. temperatureThe mixture was then heated
  9. temperatureunder reflux for 2 h before it
  10. additiondiluted with ethyl acetate (200 mL)
  11. washwashed with water (2×200 mL)
  12. customThe organic layer was separated
  13. dry with materialdried (MgSO4)
  14. filtrationthe solids filtered
  15. concentrationthe filtrate concentrated
  16. customThe residue was then purified by reverse phase HPLC

Sources & evidence

ORD record
ord-9558ef6296c940d6bb665eba4aa13610
Source dataset
uspto-grants-2004_01
Patent number
US06683103B2

Reaction notes

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