合成路线1

Condensation of 1,1,1-trifluoro-2,4-pentanedione (I) with 3-bromophenylhydrazine (II) produced an 88:12 mixture of regioisomeric pyrazoles (III) and (IV). Treatment of this mixture with copper cyanide in boiling NMP afforded the corresponding mixture of nitriles, from which the desired major isomer (V) was isolated by flash chromatography. Radical bromination of (V), followed by hydrolysis of the resulting bromomethylpyrazole (VI) with CaCO3 in aqueous dioxan, yielded alcohol (VII). Oxidation of (VII) to carboxylic acid (VIII) was then effected by treatment with sodium periodate in the presence of ruthenium trichloride. After conversion of (VIII) to the corresponding acid chloride (IX) with oxalyl chloride, coupling with 4-bromo-2-fluoroaniline (X) furnished amide (XI). Subsequent Suzuki coupling of (XI) with 2-(methylsulfanyl)phenylboronic acid (XII) gave rise to biphenyl derivative (XIII). The sulfide group of (XIII) was then oxidized to sulfone (XIV) using meta-chloroperbenzoic acid. Finally, catalytic hydrogenation of the cyano group of (XIV) over Pd/C yielded the title primary amine.