合成路线1

Reaction of 3,4-bis(trifluoromethyl)benzonitrile (I) with NaSH by means of MgCl2 in DMF gives 3,5-bis(trifluoromethyl)benzothioamide (II), which by cyclization with hydrazine hydrate (III) and HCOOH in DMF provides 3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazole (IV). Esterification of propiolic acid (V) with i-PrOH in the presence of BF3·Et2O at 90 °C affords isopropyl propiolate (VI), which is iodinated with NaI in AcOH at 110 °C to obtain isopropyl (Z)-3-iodoacrylate (VII). Condensation of triazole derivative (IV) with isopropyl (Z)-3-iodoacrylate (VII) in the presence of DABCO in DMF yields intermediate (VIII), which is subjected to ester hydrolysis with LiOH in H2O/THF to provide the corresponding carboxylic acid (IX). Finally, acid (IX) is coupled with 2-hydrazinopyrazine (X) in the presence of T3P and DIEA in CH2Cl2/EtOAc .