合成路线1

Addition of 2,5-difluorophenylmagnesium bromide (I) to the O-tetrahydropyranyl lactic acid amide (II) afforded the propiophenone derivative (III). Oxirane (IV) was then obtained by reaction of ketone (III) with the sulfur ylide generated from trimethylsulfoxonium iodide and either NaH or BuLi. Epoxide ring opening with the sodium salt of 1,2,4-triazole (V) led to the triazolyl alcohol (VI) as a mixture of diastereoisomers. After acid hydrolysis of the tetrahydropyranyl protecting group of (VI), the resultant mixture of diols was separated by column chromatography. The desired (R,R) diastereoisomer (VII) was converted to epoxide (IX) via formation of mesylate (VIII), which was subsequently cyclized in the presence of NaOMe. Nitrile (X) was then obtained by reaction of oxirane (IX) with either trimethylsilyl cyanide, followed by desilylation with Bu4NF, or with acetone cyanohydrin and LiH. Conversion of nitrile (X) into thioamide (XI) was accomplished by treatment with diethyl dithiophosphate. Cyclization of thioamide (XI) with 4-cyanophenacyl bromide (XII) gave rise to the thiazole derivative (XIII).