反应详情

温度

110 °C

A mixture of 5,7-dichloro-1,6-napthyridine (1 eq, 1 wt), 1,1-dimethylethyl (3R)-3-(aminomethyl)-3-fluoro-1-piperidinecarboxylate (1.1 eq, 1.28 wt), and diisopropylethylamine (2 eq, 1.75 vol) in NMP (6 vol) is stirred at 110±5° C. for 17 h. The solution is cooled to 70-75° C. and water (6 vol) added over 47 min at 65-75° C. The mixture is aged at 65-75° C. for 50 min, then cooled to 45° C. to give a slurry. The mixture is slowly cooled to 20-25° C. then aged for 2.25 h. The solid is collected under suction. The filter cake is washed with 1:2 v/v NMP/water (2 vol) then water (2×4 vol) and dried in vacuo at 40±5° C. As the solid still contains significant NMP (16.2% w/w) it is reslurried in 1:1 v/v NMP/water (7.3 vol). The slurry is heated to 65° C. and stirred at 65-66° C. for 1 h. The slurry is cooled to 20-25° C. and aged for 3 days. The solid is collected under suction. The filter cake is washed with 1:2 v/v NMP/water (2 vol) then water (2×4 vol) and dried in vacuo at 40±5° C.

1. temperatureThe solution is cooled to 70-75° C.
2. waitThe mixture is aged at 65-75° C. for 50 min
3. temperaturecooled to 45° C.
4. customto give a slurry
5. temperatureThe mixture is slowly cooled to 20-25° C.
6. waitthen aged for 2.25 h
7. customThe solid is collected under suction
8. washThe filter cake is washed with 1:2 v/v NMP/water (2 vol)
9. dry with materialwater (2×4 vol) and dried in vacuo at 40±5° C
10. temperatureThe slurry is heated to 65° C.
11. stirringstirred at 65-66° C. for 1 h
12. temperatureThe slurry is cooled to 20-25° C. and aged for 3 days
13. customThe solid is collected under suction
14. washThe filter cake is washed with 1:2 v/v NMP/water (2 vol)
15. dry with materialwater (2×4 vol) and dried in vacuo at 40±5° C.