反应详情

温度

80 °C

K3PO4 (5.70 g, 26.8 mmol), 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (3.73 g, 13.42 mmol) and Pd(PPh3)4 (0.517 g, 0.447 mmol) were added to a solution of 6-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 32.2, 4.0 g, 8.95 mmol) in toluene (45 mL) added under an argon atmosphere and the RM was stirred at 80° C. for 5 h. The RM was filtered through Hyflo®, which was washed with EtOAc. The filtrate and washings were combined and the solvent was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (Silica gel column, 80 g, n-hexane/EtOAc from 9:1 to 1:1) and triturated under n-hexane, filtered and dried to afford a solid, a portion of which (1.5 g, 3.02 mmol) was treated with TFA (1.163 mL, 15.10 mmol) in DCM (20 mL) and stirred at RT for 4 h. TFA (1.16 mL) was added and the mixture was allowed to stand for 3 days at RT. The solvent was evaporated off under reduced pressure and the residue was diluted with EtOAc, treated with sat. aq. Na2CO3 and extracted with EtOAc. The combined organic layers were washed with brine (50 mL), dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a crude product which was purified by flash chromatography (Silica gel column, 40 g, n-hexane/EtOAc from 9:1 to 1:1) to afford the title product as beige crystals. UPLC-MS (Condition 3) tR=1.02 min, m/z=383.1 [M+H]+.

1. additionadded under an argon atmosphere
2. filtrationThe RM was filtered through Hyflo®, which
3. washwas washed with EtOAc
4. customthe solvent was evaporated off under reduced pressure
5. customto give a residue which
6. customwas purified by flash chromatography (Silica gel column, 80 g, n-hexane/EtOAc from 9:1 to 1:1)
7. customtriturated under n-hexane
8. filtrationfiltered
9. customdried
10. customto afford a solid
11. stirringstirred at RT for 4 h
12. waitto stand for 3 days at RT
13. customThe solvent was evaporated off under reduced pressure
14. additionthe residue was diluted with EtOAc
15. additiontreated with sat. aq. Na2CO3
16. extractionextracted with EtOAc
17. washThe combined organic layers were washed with brine (50 mL)
18. dry with materialdried over Na2SO4
19. customthe solvent was evaporated off under reduced pressure
20. customto give a crude product which
21. customwas purified by flash chromatography (Silica gel column, 40 g, n-hexane/EtOAc from 9:1 to 1:1)