Dimethylformamide → HCID 58778584, compound

To a suspension of 4-fluoro-1-methylindole-3-carboxylic acid (700 mg, 3.62 mmol) and DMF (28.0 μl, 0.36 mmol) in methylene chloride (20 ml) was added oxalyl chloride (0.35 ml, 3.99 mmol) in portions under stirring at room temperature. After the reaction mixture was stirred at room temperature for 50 minutes, oxalyl chloride (30 μl) was added, and the mixture was stirred for further 40 minutes. To the reaction mixture, a solution of ethyl (4-amino-5-chloro-2-fluorophenyl)acetate (839 mg, 3.62 mmol) and triethylamine (1.52 ml, 10.9 mmol) in methylene chloride (5 ml) was added and the mixture was heated under reflux at room temperature for 4 hours. After cooling to room temperature, the reaction mixture was added with water, followed by extraction with chloroform. The extract was washed with brine, dried over anhydrous sodium sulfate, and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography opn a silica gel column, whereby from n-hexane-ethyl acetate (2:1, v/v) eluate fractions, ethyl (5-chloro-2-fluoro-4-((4-fluoro-1-methyl-3-indolylcarbonyl)amino)phenyl)acetate (762 mg, 52%) was obtained as a yellow solid.

1. stirringAfter the reaction mixture was stirred at room temperature for 50 minutes
2. stirringthe mixture was stirred for further 40 minutes
3. temperaturethe mixture was heated
4. temperatureunder reflux at room temperature for 4 hours
5. temperatureAfter cooling to room temperature
6. extractionfollowed by extraction with chloroform
7. washThe extract was washed with brine
8. dry with materialdried over anhydrous sodium sulfate
9. distillationdistilled under reduced pressure
10. customto remove the solvent
11. customThe residue was purified by chromatography opn a silica gel column, whereby from n-hexane-ethyl acetate (2:1

ORD record

ord-9ef4e488fa0941d596f58d7f864149ad

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07157487B2