The reaction of L-phenylalanine methyl ester (I) with phosgene and pyridine in dichloromethane gives the isocyanate (II) (1), which is condensed with 5-amino-1,3,4-thiadiazol-2(3H)-thione (III) in THF to yield the urea (IV). Finally, this compound is treated with methylamine in ethanol to affords the target compound.
Pentafluorophenylalanine methyl ester (I) was treated with phosgene and pyridine to afford isocyanate (II), which was condensed with 5-aminothiadiazole-2-thione (III) to provide urea (IV). Then, displacement of the ester function of (IV) with 1-(2-pyridyl)piperazine (V) furnished the title amide.
Pentafluorophenylalanine methyl ester (I) was treated with phosgene and pyridine to afford isocyanate (II), which was condensed with 5-aminothiadiazole-2-thione (III) to provide urea (IV). Then, displacement of the ester function of (IV) with methylamine furnished the title amide.
A mixture of cis and trans 4-hydroxycyclohexanecarboxylic acids (II), obtained by basic hydrolysis of the corresponding ethyl ester (I), was alkylated with pentamethylbenzyl chloride (III) in the presence of Et3N to afford pentamethylbenzyl ester (IV). Recrystallization from methylene chloride/hexane provided pure cis isomer, which was converted to 4-nitrobenzenesulfonate (VI) with p-nitrobenzenesulfonyl chloride (V) and Et3N. Subsequent displacement of the sulfonate group of (VI) for a 18F- provided the labeled intermediate (VII). Then, cleavage of the benzyl ester of (VII) with trifluoroacetic acid, followed by treatment with dichloromethyl methyl ether gave trans 4-18fluorocyclohexanecarbonyl chloride (VIII). This was finally coupled with amine (WAY-100634)(IX) in the presence of Et3N in CH2Cl2 to produce the target amide.