E-5842

Chemical Name: 4-(4-Fluorophenyl)-1-[4-(1,2,4-triazol-1-yl)butyl]-1,2,3,6-tetrahydropyridine citrate
CAS No. 177945-46-9 (free base), 177945-45-8 (HCl)
项目整合开发状态: Phase II
项目研究机构: Esteve (Originator)
合成路线:E-5842 was prepared by reacting (I) with citric acid monohydrate in ethanol.The base (I) can be obtained by two ways:1) By condensation of 4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine (III) or 8-(4-fluorophenyl)-5-azoniaspiro[4.5]dec-7-ene chloride (IV) with 1-(4-chlorobutyl)-1H-1,2,4-triazole (V) or 1H-1,2,4-triazole,respectively,in dimethylformamide in the presence of potassium hydrogencarbonate.2) By dehydration of 1-[4-[4-(4-fluorophenyl)-4-hydroxy-1-piperidyl]butyl]-1H-1,2,4-triazole (VI) in refluxing hydrochloric acid/ethanol.The piperidinol (VI) can be obtained by two procedures:a) By condensation of 4-(4-fluorophenyl)-4-hydroxypiperidine (II) with 1-(4-chlorobutyl)-1H-1,2,4-triazole (V) in dimethylformamide in the presence of potassium hydrogencarbonate.b) By condensation of 1,4-dioxa-8-azaspiro[4.5]decane (VII) with 1-(4-chlorobutyl)-1H-1,2,4-triazole (V) and hydrolysis of the acetal to give 1-[4-(4-oxo-1-piperidyl)butyl]-1H-1,2,4-triazole (VIII),followed by addition of 4-fluorophenyllithium or 4-fluorophenyl magnesium bromide in ether or tetrahydrofuran to yield (VI).