新产品编号:19493

5-氯-1-(4-氯苄基)-3-(苯基硫基)-1H-吲哚-2-羧酸Chemical Name: 5-Chloro-1-(4-chlorobenzyl)-3-(phenylsulfanyl)-1H-indole-2-carboxylic acid
CAS No. 118414-59-8
项目整合开发状态: Preclinical
项目研究机构: Merck & Co. (Originator)
合成路线:The condensation of 6-fluoro-2-methylindole (I) with beta-chloropropionitrile (II) by means of ethylmagnesium iodide (that forms the magnesium salt of (I)) in refluxing ether gives 3-(6-fluoro-2-methyl-3-indolyl)propionitrite (III),which is hydrolyzed with KOH in refluxing water yielding 3-(6-fluoro-2-methyl-3-indolyl)propionic acid (IV) (1).The condensation of (IV) with 4-hydroxy-4-(3-trifluoromethylphenyl)piperidine (V) by means of ethyl chloroformate and triethylamine in refluxing THF affords 1-[3-(6-fluoro-2-methyl-3-indolyl)propionyl]-4-hydroxy-4-(3-trifluromethylphenyl)piperidine (VI),which is reduced with LiAlH4 in refluxing THF giving 1-[3-(6-fluoro-2-methyl-3-indolyl)propyl]-4-hydroxy-4-(3-trifluoromethylphenyl)piperidine (VII).The ozonolysis of (VII) in HOAc affords 1-[3-(2-acetamido-4-fluorobenzoyl)propyl]-4-hydroxy-4-(3-trifluoromethylphenyl)piperidine (VIII),which is finally hydrolyzed with concentrated HCl in refluxing EtOH

合成路线:Sulfenylation of the Grignard reagent derived from ethyl 5-chloroindole-2-carboxylate (I) with S-phenyl benzenethiosulfonate affords the 3-phenylsulfanyl indole (II).This is then alkylated with 4-chlorobenzyl chloride (III) in the presence of potassium hexamethyldisilazide to yield the N-benzyl indole derivative (IV).Finally,hydrolysis of ethyl ester (IV) by means of potassium trimethylsilanolate under anhydrous conditions produces the target carboxylic acid (1,2).