反应详情

A 250 mL, round-bottomed flask under a positive pressure of nitrogen was equipped with a magnetic stirrer and charged with anhydrous DMF (70 mL) followed by 2-[4-(4-amino-2-fluoro-phenyl)-piperazin-1-yl]-N,N-diethyl-2-phenyl-acetamide (3.5 g, 9.1 mmol), 2-pyridin-3-yl-benzoic acid (1.9 g, 9.5 mmol), HATU (3.8 g, 10.0 mmol) and DIPEA (1.3 g, 10.0 mmol). The resulting brown colored reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was then concentrated on the rotary evaporator to yield an oil. To this oil was added, dichloromethane (100 mL) and 1N NaOH (50 mL). The biphasic solution was stirred for 0.5 h after which phases were separated. The aqueous layer was extracted with dichloromethane (2×25 mL). The organic layers were pooled, dried over anhydrous sodium sulfate, filtered and concentrated to yield a viscous brown oil. The oil was taken in ethanol (100 mL) and heated to ˜60° C. in a water bath for 1 h. The resulting mixture was diluted with MTBE (added with magnetic stirring in 25 mL portions, total 125 mL). The resulting suspension was stirred at 0° C. (ice/water bath) for 2 h. The product was collected by filtration through a medium porosity glass frit, washed with a mixture of EtOH/MTBE (1:1.25, 22.5 mL×2) and the filter-cake dried thoroughly under house vacuum to yield the title compound as an off-white solid.

1. customA 250 mL, round-bottomed flask under a positive pressure of nitrogen was equipped with a magnetic stirrer
2. concentrationThe reaction mixture was then concentrated on the rotary evaporator
3. customto yield an oil
4. additionTo this oil was added
5. stirringThe biphasic solution was stirred for 0.5 h after which phases
6. customwere separated
7. extractionThe aqueous layer was extracted with dichloromethane (2×25 mL)
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customto yield a viscous brown oil
12. temperatureheated to ˜60° C. in a water bath for 1 h
13. filtrationThe product was collected by filtration through a medium porosity glass frit
14. washwashed with a mixture of EtOH/MTBE (1:1.25, 22.5 mL×2)
15. customthe filter-cake dried thoroughly under house vacuum