Thionyl Chloride → 5-Acetyl-thiophene-2-carboxylic acid [4-(2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide

Temperature

79 °C

A dry 100 mL flask was charged with 5-Acetyl-thiophene-2-carboxylic acid (0.9339 g, 5.49 mmol) and thionyl chloride (6 mL) and allowed to stir at 79° C. for 2 h. The thionyl chloride was then removed by concentration in vacuo. The crude acid chloride was cooled to room temperature, and then dissolved in THF (80 mL). 6-(4-Amino-benzoyl)-1,3-dihydro-indol-2-one (as prepared in Example 15, 1.00 g, 3.97 mmol) was added to the THF solution of the acid chloride, and the mixture was allowed to reflux for 4 h. The reaction mixture was then allowed to cool to room temperature. The room temperature reaction mixture was concentrated in vacuo. The solid residue was suspended in boiling EtOAc. The suspension was allowed to cool to room temperature before filtering to afford the 5-Acetyl-thiophene-2-carboxylic acid [4-(2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide as a solid (1.16 g, 3.94 mmol, 99%).

1. customThe thionyl chloride was then removed by concentration in vacuo
2. temperatureThe crude acid chloride was cooled to room temperature
3. dissolutiondissolved in THF (80 mL)
4. temperatureto reflux for 4 h
5. temperatureto cool to room temperature
6. customThe room temperature reaction mixture
7. concentrationwas concentrated in vacuo
8. temperatureto cool to room temperature
9. filtrationbefore filtering

ORD record

ord-7cb0a81d87ee4e9c8aed5cf3fbd249ad

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07749530B2