Triethylamine → Ethyl (5-chloro-2-fluoro-4-(((5-fluoro-1-methyl-3-indolyl)carbonyl)amino)phenyl)acetate

HRID 1372707

반응식

HRID 1372707 반응식
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[CH:6]=[C:5]2[C:12]([OH:14])=O.C(Cl)(=O)C(Cl)=O.[NH2:21][C:22]1[C:27]([Cl:28])=[CH:26][C:25]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:24]([F:35])[CH:23]=1.C(N(CC)CC)C>C(Cl)Cl.Cl>[Cl:28][C:27]1[C:22]([NH:21][C:12]([C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=3)[N:7]([CH3:11])[CH:6]=2)=[O:14])=[CH:23][C:24]([F:35])=[C:25]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH:26]=1

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 17858807Ethyl 4-amino-5-chloro-2-fluorophenylacetateHCID 183851025-fluoro-1-methyl-1H-indole-3-carboxylic acid

생성물 1

HCID 58778397Ethyl (5-chloro-2-fluoro-4-(((5-fluoro-1-methyl-3-indolyl)carbonyl)amino)phenyl)acetate수율 47%

시약·촉매·용매 2

HCID 313Hydrochloric Acid용매HCID 6344Dichloromethane용매2회

반응 조건

온도
0 °C

실험 절차

In methylene chloride (30 ml) was dissolved 5-fluoro-1-methylindole-3-carboxylic acid (885 mg, 4.58 mmol). To the resulting solution was added oxalyl chloride (600 μl, 6.87 mmol) under stirring at 0° C., and the resulting mixture was stirred at room temperature for 1 hour. From the reaction mixture, the solvent was distilled off under reduced pressure. The residue was dissolved in methylene chloride (50 ml). The resulting solution was added dropwise to a solution of ethyl (4-amino-5-chloro-2-fluorophenyl)acetate (1.06 g, 4.58 mmol) in methylene chloride (20 ml), followed by heating under reflux for 15 minutes. The reaction mixture was cooled and triethylamine (3.19 ml, 22.9 mmol) was added thereto. The resulting mixture was heated under reflux for 18 hours. The reaction mixture was cooled and poured in 1N HCl, followed by extraction with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from hexane/ethyl acetate (2/1) eluate fractions, ethyl (5-chloro-2-fluoro-4-(((5-fluoro-1-methyl-3-indolyl)carbonyl)amino)phenyl)acetate (868 mg, 47%) was obtained as a white solid.

후처리

  1. stirringthe resulting mixture was stirred at room temperature for 1 hour
  2. distillationFrom the reaction mixture, the solvent was distilled off under reduced pressure
  3. dissolutionThe residue was dissolved in methylene chloride (50 ml)
  4. temperatureby heating
  5. temperatureunder reflux for 15 minutes
  6. temperatureThe reaction mixture was cooled
  7. temperatureThe resulting mixture was heated
  8. temperatureunder reflux for 18 hours
  9. temperatureThe reaction mixture was cooled
  10. extractionfollowed by extraction with ethyl acetate
  11. dry with materialThe extract was dried over anhydrous sodium sulfate
  12. distillationdistilled under reduced pressure
  13. customto remove the solvent
  14. customThe residue was purified by chromatography on a silica gel column, whereby from hexane/ethyl acetate (2/1) eluate fractions

출처 및 근거

ORD 기록
ord-9a7ef896ad7749caa06334d43bd175d7
출처 데이터셋
uspto-grants-2007_01
특허 번호
US07157487B2

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