反应详情

温度

0 °C

With stirring, 3.85 g (41.34 mmol) of aniline were added to water (40 ml) and conc. hydrochloric acid (7.07 ml), and this mixture was cooled to 0° C. A solution of 2.85 g (41.34 mmol) of sodium nitrite in water (21 ml) was then added dropwise at between 0° C. and 5° C., followed by stirring at 0° C. for 15 min. Thereafter, at 0° C., a solution of 4.28 g (52.25 mmol) of sodium acetate in water (19 ml) was rapidly added dropwise, and then, with good stirring, a solution of 2.73 g (41.34 mmol) of malononitrile in ethanol (10 ml) was added dropwise. After 2 h at 0° C., the resulting precipitate was filtered off with suction and washed three times with water (50 ml each time) and with petroleum ether (50 ml). The still-moist residue was dissolved in DMF (46 ml) and added dropwise at exactly 85° C. to a solution of 9.5 g (33.07 mmol) of 5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboximidamide acetate (example 28A) in DMF (46 ml) and triethylamine (5.76 ml). The mixture was then stirred at 100° C. for 4 h and left to cool to RT overnight. The mixture was poured onto water (480 ml) and extraction was effected by stirring at RT for 1 h. After the precipitate had been filtered off with suction, it was washed twice with water (100 ml each time) and twice with methanol (50 ml each time) and then dried under high vacuum.

1. stirringby stirring at 0° C. for 15 min
2. filtrationthe resulting precipitate was filtered off with suction
3. washwashed three times with water (50 ml each time)
4. dissolutionThe still-moist residue was dissolved in DMF (46 ml)
5. stirringThe mixture was then stirred at 100° C. for 4 h
6. waitleft
7. temperatureto cool to RT overnight
8. additionThe mixture was poured onto water (480 ml) and extraction
9. stirringby stirring at RT for 1 h
10. filtrationAfter the precipitate had been filtered off with suction, it
11. washwas washed twice with water (100 ml each time) and twice with methanol (50 ml each time)
12. customdried under high vacuum