FJ-5002

Chemical Name: 3-Ethyl-2-[3-ethyl-5-(3-methyl-2,3-dihydrobenzothiazol-2-ylidene)-4-oxo-2,3,4,5-tetrahydrothiazol-2-ylidenemethyl]-4-methyl-3-thiazolium chloride
CAS No. 147366-40-3, 199916-89-7 (acetate), 199916-88-6 (cation)
项目整合开发状态: Preclinical
项目研究机构: Dana-Farber Cancer Institute (Originator), Fuji Photo Film (Originator)
合成路线:The alkylation of 2-(methylsulfanyl)benzothiazole (I) with methyl p-toluenesulfonate in anisole gives 3-methyl-2-(methylsulfanyl)benzothiazolium p-toluenesulfonate (II),which is condensed with 3-ethyl-2-thioxothiazolidin-4-one (III) by means of triethylamine in acetonitrile to yield 3-ethyl-5-(3-methyl-2,3-dihydrobenzothiazol-2-ylidene)-2-thioxothiazolidin-4-one (IV).The methylation of (IV) with methyl p-toluenesulfonate in DMF affords 3-ethyl-5-(3-methyl-2,3-dihydrobenzothiazol-2-ylidene)-2-(methylsulfanyl)-4-oxo-4,5-dihydrothiazolium p-toluenesulfonate (V) (1),which is condensed with 1-ethyl-2-methylpyridinium p-toluenesulfonate (VI) by means of triethylamine in warm acetonitrile giving the p-toluenesulfonate of MKT-077 (VII).Finally,this compound is passed through an ion-exchange resin (Amberlyst A-26) in methanol/chloroform.

合成路线:N-Methylation of 2-(methylsulfanyl)benzothiazole (I) using methyl p-toluenesulfonate afforded iminium salt (II),which was condensed with 3-ethyl-4-oxothiazolidine-2-thione (III) to give the benzothiazolinylidene dervative (IV).Subsequent S-methylation of (IV) to produce the 3-ethyl-2-(methylthio)thiazolinium salt (V) was followed by condensation with 2,4-dimethyl-3-ethylthiazolium salt (VI) in the presence of Et3N,yielding the triheterocyclic system (VIII) as the p-toluenesulfonate salt.Finally,conversion to the title chloride salt was achieved by means of an anionic exchange resin.