反应详情

348 mg (1.7 mmol) of the compound from Example 3A and 300 mg (1.7 mmol) of the compound from Example 11A are initially introduced into a mixture of 6 ml THF and 6 ml ethanol. 63 mg (0.3 mmol) p-toluenesulfonic acid monohydrate are added and the mixture is reacted in a single mode microwave (CEM Explorer) at 130° C. for 1.5 h. The mixture is allowed to cool to RT, a further 50 mg of the compound from Example 3A and a spatula-tip of p-toluenesulfonic acid monohydrate are added and the mixture is heated at 150° C. for 1 h. It is allowed to cool to room temperature and is decanted off from the solid and the solid is washed several times with THF (solid batch 1). The supernatant decanted off and the wash solution are combined, the mixture is concentrated and 5 ml ethanol and 5 ml THF and a spatula-tip of p-toluenesulfonic acid monohydrate are added to the residue obtained. The mixture is reacted again in a single mode microwave (CEM Explorer) at 150° C. for 2 h. It is allowed to cool to RT and the solid formed is filtered off (solid batch 2). The filtrate is concentrated, 3 ml DMSO are added to the residue and purification is carried out by means of preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). The product-containing fractions are combined and concentrated. The residue is dissolved in ethanol, a little THF is added and the mixture is concentrated, with formation of a precipitate. The solid is filtered off and washed with THF (solid batch 3). The three solid batches obtained are combined and the mixture is dried under a high vacuum.

1. customthe mixture is reacted in a single mode microwave (CEM Explorer) at 130° C. for 1.5 h
2. temperaturethe mixture is heated at 150° C. for 1 h
3. temperatureto cool to room temperature
4. customis decanted off from the solid
5. washthe solid is washed several times with THF (solid batch 1)
6. customThe supernatant decanted off
7. concentrationthe mixture is concentrated
8. addition5 ml ethanol and 5 ml THF and a spatula-tip of p-toluenesulfonic acid monohydrate are added to the residue
9. customobtained
10. customThe mixture is reacted again in a single mode microwave (CEM Explorer) at 150° C. for 2 h
11. temperatureto cool to RT
12. customthe solid formed
13. filtrationis filtered off (solid batch 2)
14. concentrationThe filtrate is concentrated
15. addition3 ml DMSO are added to the residue and purification
16. additionis carried out by means of preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% TFA)
17. concentrationconcentrated
18. dissolutionThe residue is dissolved in ethanol
19. additiona little THF is added
20. concentrationthe mixture is concentrated, with formation of a precipitate
21. filtrationThe solid is filtered off
22. washwashed with THF (solid batch 3)
23. customThe three solid batches obtained
24. customthe mixture is dried under a high vacuum