反应详情

温度

60 °C

1 g (1.9 mmol) of benzotriazol-1-yloxytris(pyrrolidine)phosphonium hexafluorophosphate is added, with stirring and under nitrogen, to a suspension of 0.5 g (1.74 mmol) of 5-fluoro-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxylic acid, obtained in step 11.1, in 10 ml of dry dimethylformamide. After 5 minutes, 0.4 g (1.83 mmol) of 7-aminoquinoline hydrochloride (WO 2003/049702) and 0.9 g (7 mmol) of diisopropylethylamine are added. After stirring for 2 hours at room temperature and for 2 hours at 60° C., the reaction medium is poured into 100 ml of water and 50 ml of ethyl acetate. After separation of the phases by settling and extraction of the aqueous phase, the organic phases are combined, washed with water and dried over sodium sulfate. The residue is purified by chromatography on a column of silica gel, eluting with a mixture of dichloromethane and acetone. The solid obtained is recrystallized from isopropyl alcohol. 0.26 g of solid is obtained.

1. customAfter separation of the phases
2. extractionextraction of the aqueous phase
3. washwashed with water
4. dry with materialdried over sodium sulfate
5. customThe residue is purified by chromatography on a column of silica gel
6. washeluting with a mixture of dichloromethane and acetone
7. customThe solid obtained
8. customis recrystallized from isopropyl alcohol