4-Fluoroiodobenzene → HCID 178519322, 화합물

참여 물질

반응 조건

반응 단계

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%).

출처 및 근거