反应详情

温度

80 °C

0.75 ml of 2 M aqueous sodium carbonate solution and 20.3 mg (0.02 mmol) of PdCl2(dppf) are added to a mixture of 200 mg (0.50 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 8A) and 89.1 mg (0.50 mmol) of 3-(acetamido)phenylboronic acid in 2 ml of DMF. The reaction mixture is heated at 80° C. for 17 h. A further 89.1 mg (0.50 mmol) of 3-(acetamido)phenylboronic acid, 1.5 ml of 1N sodium hydroxide solution and 81.3 mg (0.1 mmol) of PdCl2(dppf) are added, and the mixture is heated at 86° C. for a further 18 h. After cooling, it is filtered through kieselguhr and purified by preparative HPLC. The resulting crude product is further purified by flash chromatography on silica gel (mobile phase: dichloromethane/methanol/ammonia 100:10:2). The product fractions are concentrated, taken up in a 5:1-mixture of methanol and 1N hydrochloric acid and again concentrated. Drying under high vacuum results in 243.2 mg (86.6% of theory) of the title compound.

1. temperaturethe mixture is heated at 86° C. for a further 18 h
2. temperatureAfter cooling
3. filtrationit is filtered through kieselguhr
4. custompurified by preparative HPLC
5. customThe resulting crude product is further purified by flash chromatography on silica gel (mobile phase: dichloromethane/methanol/ammonia 100:10:2)
6. concentrationThe product fractions are concentrated
7. concentration1-mixture of methanol and 1N hydrochloric acid and again concentrated
8. customDrying under high vacuum