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Triethylamine → N-(3,4,5-Trimethoxyphenyl)-3-(5-methyl-3-(2-iodo-6-fluoro-phenyl)isoxazol-4-oyl)aminophenyl Acetamide

HRID 434056
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HRID 434056 반응식
[C:1]([C:4]1[C:5]([C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[I:17])=[N:6][O:7][C:8]=1[CH3:9])([OH:3])=O.C(Cl)(=O)C(Cl)=O.[NH2:24][C:25]1[CH:26]=[C:27]([CH2:31][C:32]([NH:34][C:35]2[CH:40]=[C:39]([O:41][CH3:42])[C:38]([O:43][CH3:44])=[C:37]([O:45][CH3:46])[CH:36]=2)=[O:33])[CH:28]=[CH:29][CH:30]=1.C(N(CC)CC)C>ClCCl.C1COCC1.CN(C=O)C>[CH3:42][O:41][C:39]1[CH:40]=[C:35]([NH:34][C:32](=[O:33])[CH2:31][C:27]2[CH:28]=[CH:29][CH:30]=[C:25]([NH:24][C:1]([C:4]3[C:5]([C:10]4[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=4[I:17])=[N:6][O:7][C:8]=3[CH3:9])=[O:3])[CH:26]=2)[CH:36]=[C:37]([O:45][CH3:46])[C:38]=1[O:43][CH3:44]
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참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 179306454-Carboxy-5-methyl-3-(2-iodo-6-fluoro-phenyl)isoxazoleHCID 187562602-(3-aminophenyl)-N-(3,4,5-trimethoxyphenyl)acetamide

생성물 1

HCID 70026384N-(3,4,5-Trimethoxyphenyl)-3-(5-methyl-3-(2-iodo-6-fluoro-phenyl)isoxazol-4-oyl)aminophenyl Acetamide수율 51.7%

시약·촉매·용매

3
HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

To a solution of 4-carboxy-5-methyl-3-(2-iodo-6-fluoro-phenyl)isoxazole (1.75 g, 5 mmol) in dichloromethane (30 ml) and THF (1 ml) was added oxalyl chloride (0.88 ml, 10 mmol, 2 eq.) under N2, then DMF (3 drops) to initiate the reaction. The reaction was stirred for 2 h, concentrated, and re-dissolved in dichloromethane (50 ml) under N2. A solution of 2-(3-aminophenyl)-N-(3,4,5-trimethoxyphenyl)acetamide (1.59, 5 mmol) in THF (14 ml) was added, cooled to 0° C., and then added triethylamine (0.7 ml, 5 mmol), and stirred for 17 h. Crude reaction was partitioned between ethyl acetate and 1N HCl. The organic layer was washed with H2O and brine, dried (MgSO4), filtered and concentrated. The crude material was titrated with diethyl ether (3×) and purified by flash chromatography (silica gel) using 1-10% acetone in dichloromethane to give the title compound (1.67 g, 51%).

후처리

  1. customthe reaction
  2. concentrationconcentrated
  3. dissolutionre-dissolved in dichloromethane (50 ml) under N2
  4. customCrude reaction
  5. customwas partitioned between ethyl acetate and 1N HCl
  6. washThe organic layer was washed with H2O and brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by flash chromatography (silica gel)

출처 및 근거

ORD 기록
ord-820dd343512d42b9afcdd38fd9b57cd6
출처 데이터셋
uspto-grants-2003_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06670373B1

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