合成路线1

3-Trifluoromethyl-4-nitrophenylisocyanate (I) and 2-amino-2-cyanopropane (II) are condensed. After concentration by distillation under reduced pressure and chromatography of the residue on silica gel (elution with dichloromethane: acetone, 8:2 v/v), the intermediate 1-(3'-trifluoromethyl-4'-nitrophenyl)-4,4-dimethyl-5-imino-2-imidazolidinone) (III) is obtained. This intermediate, in suspension in aqueous hydrochloric acid, is heated, then cooled and poured into water. The precipitate, filtered, washed and dried, is anandron (RU-23908), which can be recrystallized in an ethanolic medium.

合成路线2

The reaction of 4-cyano-3-(trifluoromethyl)aniline (I) with phosgene afforded isocyanate (II). Subsequent condensation with 2-amino-2-methylpropionitrile (III) in the presence of Et3N in dichloroethane yielded the iminoimidazolidinone (IV), which was hydrolyzed to hydantoin (V) with refluxing 0.5 M HCl. Finally, alkylation with bromoacetonitrile (VI) in the presence of NaH in DMF provided the cyanomethyl compound.

合成路线3

The bicyclic nitrile (III) was prepared by reaction of 1,7-dichloroheptan-4-one (I) with 2-aminoisobutyronitrile (II) in the presence of methanolic ammonia (1). Addition of 2-adamantyllithium (IV) to nitrile (III) in Et2O at -50 C furnished ketone (V). Subsequent addition of 4-fluorophenylmagnesium bromide (VI) to ketone (V) in cold THF provided the desired carbinol, which was isolated as the corresponding hydrochloride salt by lyophilization of its solution in aqueous HCl.

合成路线4