新产品编号:1166443

Chemical Name: N-[2-(Pentafluorophenyl)-1(S)-[4-(2-pyridyl)piperazin-1-ylcarbonyl]ethyl]-N'-(5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)urea
项目整合开发状态: Biological Testing
项目研究机构: Pfizer (Originator)
合成路线: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.

合成路线: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.

合成路线: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.

合成路线: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.