反应详情

Heat a solution of 3-amino-6-fluoro-benzo[b]thiophene-2-carboxylic acid (5.0 g, 24 mmol) in 1-methyl-2-pyrrolidinone (5 ml) to 100° C. for 2 h., and then, introduce a stream of nitrogen, to cool the solution to room temperature. Add homopiperazine (9.5 g, 95 mmol) and p-toluene sulfonic acid monohydrate (9.0 g, 47 mmol) and heat the mixture to 145° C. for 4 h. After that time, cool the reaction mixture to room temperature, dilute with ethyl acetate (30 mL) and wash with brine (3×15 mL). Separate the organic layer and dry over MgSO4. Evaporate the solvent and purify the crude product by column chromatography (SiO2, 100 g CH2Cl2/MeOH 9:2, then

1. additionintroduce a stream of nitrogen
2. temperatureAfter that time, cool the reaction mixture to room temperature
3. washwash with brine (3×15 mL)
4. customSeparate the organic layer
5. dry with materialdry over MgSO4
6. customEvaporate the solvent
7. custompurify the crude product by column chromatography (SiO2, 100 g CH2Cl2/MeOH 9:2