反应详情

154 mg (0.37 mmol) of 6-[amino(hydroxyimino)methyl]-N-[(3R)-1-azabicyclo[2.2.2]-oct-3-yl]-1-benzothiophene-2-carboxamide dihydrochloride (Example 27A) are dissoved in 2 ml of DMF and 0.75 ml of THF. 250 mg of 4 Å molecular sieves are added, and the mixture is stirred at room temperature for 30 min. Addition of 44.4 mg (1.11 mmol) of sodium hydride (60% suspension in mineral oil) is followed by heating at 60° C. for 20 min and then cooling to room temperature. A solution of 90 μl (1.11 mmol) of methyl acetate in 1 ml of THF is then added to the reaction mixture, after which it is heated at 80° C. for 14 h. Addition of a further 29.6 mg (0.74 mmol) of sodium hydride (60% suspension in mineral oil) and 0.88 ml (11.1 mmol) of methyl acetate in 1 ml of THF is followed by heating at 70° C. for a further 24 h. The reaction is stopped by adding water. Purification takes place by preparative HPLC. The product fractions are concentrated and, after addition of a 5:1 mixture of methanol and 4N hydrogen chloride in dioxane, again concentrated. Drying under high vacum results in 41.9 mg (23.6% of theory) of the title compound.

1. addition250 mg of 4 Å molecular sieves are added
2. temperatureby heating at 60° C. for 20 min
3. temperaturecooling to room temperature
4. temperatureafter which it is heated at 80° C. for 14 h
5. temperatureby heating at 70° C. for a further 24 h
6. customPurification
7. concentrationThe product fractions are concentrated
8. additionafter addition of a 5:1 mixture of methanol and 4N hydrogen chloride in dioxane
9. concentrationagain concentrated
10. customDrying under high vacum