Dimethylformamide → Ethyl (5-chloro-2-fluoro-4-((6-fluoro-1-methyl-3-indolylcarbonyl)amino)phenyl)acetate

HRID 1372703

Reaktionsgleichung

Reaktionsgleichung von HRID 1372703
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]([OH:14])=O)=[CH:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[NH2:26][C:27]1[C:32]([Cl:33])=[CH:31][C:30]([CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])=[C:29]([F:40])[CH:28]=1.C(N(CC)CC)C>C(Cl)Cl>[Cl:33][C:32]1[C:27]([NH:26][C:12]([C:6]2[C:5]3[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=3)[N:8]([CH3:11])[CH:7]=2)=[O:14])=[CH:28][C:29]([F:40])=[C:30]([CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH:31]=1

Komponenten

7

Edukt 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 178587926-fluoro-1-methyl-1H-indole-3-carboxylic acidHCID 17858807Ethyl 4-amino-5-chloro-2-fluorophenylacetate

Produkt 1

HCID 58778583Ethyl (5-chloro-2-fluoro-4-((6-fluoro-1-methyl-3-indolylcarbonyl)amino)phenyl)acetateAusbeute 63,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a suspension of 6-fluoro-1-methylindole-3-carboxylic acid (500 mg, 2.59 mmol) and DMF (0.02 ml, 0.26 mmol) in methylene chloride (15 ml) was added dropwise oxalyl chloride (0.25 ml, 2.85 mmol) under stirring at room temperature. After completion of the dropwise addition, the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was then distilled under reduced pressure to remove the solvent. The residue was dissolved in methylene chloride (10.0 ml), followed by the dropwise addition to a solution of ethyl (4-amino-5-chloro-2-fluorophenyl)acetate (600 mg, 2.59 mmol) and triethylamine (1.08 ml, 7.77 mmol) in methylene chloride (5.0 ml). After completion of the dropwise addition, the reaction mixture was heated under reflux for 10 hours. After the reaction mixture was cooled to room temperature, the precipitated crystals were removed under reduced pressure. The filtrate was distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from n-hexane:ethyl acetate (2:1, v/v) eluate fractions, ethyl (5-chloro-2-fluoro-4-((6-fluoro-1-methyl-3-indolylcarbonyl)amino)phenyl)acetate (665 mg, 63%) was obtained as a yellow solid.

Aufarbeitung

  1. additionAfter completion of the dropwise addition
  2. stirringthe reaction mixture was stirred at room temperature for 1 hour
  3. distillationThe reaction mixture was then distilled under reduced pressure
  4. customto remove the solvent
  5. dissolutionThe residue was dissolved in methylene chloride (10.0 ml)
  6. additionAfter completion of the dropwise addition
  7. temperaturethe reaction mixture was heated
  8. temperatureunder reflux for 10 hours
  9. temperatureAfter the reaction mixture was cooled to room temperature
  10. customthe precipitated crystals were removed under reduced pressure
  11. distillationThe filtrate was distilled under reduced pressure
  12. customto remove the solvent
  13. customThe residue was purified by chromatography on a silica gel column, whereby from n-hexane:ethyl acetate (2:1

Quellen und Nachweise

ORD-Eintrag
ord-41dd85410c78484faf8d0c30a1a322c9
Quelldatensatz
uspto-grants-2007_01
Patentnummer
US07157487B2

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