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 2303723노트

반응식

HRID 2303723 반응식
[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]

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-ca5dd401af0b4e138c7deede1a18ef2a
출처 데이터셋
uspto-grants-2002_08
특허 번호
US06432994B1

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