反应详情

温度

30 °C

In an alternative method, 4-methylbenzenesulfinate (anhydrous, 1.2 eqv, 22.6 g, 127 mmol) was suspended in dry DMSO (20 vol, 500 ml). The stirred mixture was warmed to 30° C. under a nitrogen atmosphere. Upon complete dissolution Pd(PPh3)4 (2 mol %, 2.4 g, 2.1 mmol) was added. The mixture was stirred for 10 min at 25-30° C. after which time a turbid yellow solution was present. Allyl 2-amino-6-fluoro-pyrazolo[1,5-a]pyrimidine-3-carboxylate (25 g, 105.8 mmol) was added portionwise, maintaining the temperature at 25-30° C. Once addition was complete the cloudy solution was stirred until the reaction was complete by HPLC (2-3 hrs). A heavy precipitate formed after 15 minutes post addition of the substrate. The mixture became thicker as the reaction proceeded. The reaction mixture was diluted with water (125 ml) and 2M HCl (66 ml) was added slowly, maintaining the temperature at 25-30° C. The slurry was stirred for 30 minutes, then filtered. The filtration was slow (2 hrs). The resulting solid was washed with water, then dried on the sinter. The solid was slurried in DCM (8 vol) for 1 hr. The solid was filtered (rapid filtration) and washed with DCM. The solid was re-slurried in chloroform (8 vol) for 1 hr. The acid was filtered and dried on the sinter. It was further dried in a vacuum oven at 50° C. for 24 hrs. The product was obtained as an off-white solid (18.6 g, 85%); 1H NMR (500 MHz, DMSO-d6) δ 12.14 (1H, brs), 9.31 (1H, dd), 8.69 (1H, m), 6.47 (2H, brS); 19F NMR (500 MHz, DMSO-d6) δ−153.65; MS (ES+) 197.1.

1. additionwas added
2. temperaturemaintaining the temperature at 25-30° C
3. additionOnce addition
4. stirringwas stirred until the reaction
5. customwas complete by HPLC (2-3 hrs)
6. customA heavy precipitate formed after 15 minutes post addition of the substrate
7. additionwas added slowly
8. temperaturemaintaining the temperature at 25-30° C
9. stirringThe slurry was stirred for 30 minutes
10. filtrationfiltered
11. filtrationThe filtration
12. custom(2 hrs)
13. washThe resulting solid was washed with water
14. customdried on the sinter
15. waitThe solid was slurried in DCM (8 vol) for 1 hr
16. filtrationThe solid was filtered
17. filtration(rapid filtration)
18. washwashed with DCM
19. waitThe solid was re-slurried in chloroform (8 vol) for 1 hr
20. filtrationThe acid was filtered
21. customdried on the sinter
22. customIt was further dried in a vacuum oven at 50° C. for 24 hrs