4-Fluoroiodobenzene → HCID 178519322, compound

Temperature

80 °C

0.25 mmol of 1-fluoro-4-iodo-benzene were weighted into a reaction tube. 2.5 mmol sodium hadrogencarbonate was added as solid, followed by 0.25 mmol tetrabutylammonium fluoride in 0.5 ml DMF and 0.1 mmol of 4-[6-(4-hydroxy-phenyl)-1-(tetrahydro-pyran-2-yl)-3-vinyl-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester in 1 ml DMF. The tube was purged with Argon. 0.01 mmol palladium(II) acetate in 0.25 mmol DMF was added, the tube was closed with a screw cap and stirred for 8 h at 80° C. New palladium(II) acetate (0.01 mmol) was added and heating continued for 1 h at 100° C. The reaction mixture was diluted with 20 ml ethyl acetate and washed with 20 ml water, dried and evaporated. The residue was dissolved in 5 ml THF and 1 ml methanol and shaken with 100 mg silica-bound propane thiol scavenger for 4 h at RT. The mixture was filtered, the filter washed with THF, the filtrate evaporated and the residue submitted to SFC purification. The purified product was dissolved in 3 ml methanol and 0.5 ml 4N HCl in dioxane. The mixture was stirred for 30 min at 65° C. The cooled solution was diluted slowly with ml diethyl ether to precipitate the product, which was filtered off, washed with 1 ml diethyl ether, and dried in vacuo to afford [3-[(E)-2-(4-Fluoro-phenyl)-vinyl]-6-(4-hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-piperazin-1-yl-methanone (18 mg, 37%).

1. customThe tube was purged with Argon
2. customthe tube was closed with a screw
3. customcap
4. temperatureheating
5. waitcontinued for 1 h at 100° C
6. washwashed with 20 ml water
7. customdried
8. customevaporated
9. dissolutionThe residue was dissolved in 5 ml THF
10. stirring1 ml methanol and shaken with 100 mg silica-bound propane thiol scavenger for 4 h at RT
11. filtrationThe mixture was filtered
12. washthe filter washed with THF
13. customthe filtrate evaporated
14. customthe residue submitted to SFC purification
15. dissolutionThe purified product was dissolved in 3 ml methanol
16. stirringThe mixture was stirred for 30 min at 65° C
17. additionThe cooled solution was diluted slowly with ml diethyl ether
18. customto precipitate the product, which
19. filtrationwas filtered off
20. washwashed with 1 ml diethyl ether
21. customdried in vacuo

ORD record

ord-dd210c383e2b44b0a7bbccf413c07fab

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846712B2