反应详情

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.

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