新产品编号:210915

Chemical Name: trans-7-[4-[4-[3-(2-Methoxybenzyloxy)propoxy]phenyl]piperidin-3-yloxymethyl]-1,2,3,4-tetrahydroquinoline dihydrochloride
CAS No. 188876-00-8 (free base)
项目整合开发状态: Preclinical
项目研究机构: Roche (Originator)
合成路线:The condensation of 1-benzyl-4-piperidone (I) with 4-iodoanisole (II) in ethyl ether gives 1-benzyl-4-(2-methoxyphenyl)piperidin-4-ol (III),which is dehydrated by means of p-toluenesulfonic acid in refluxing toluene yielding the tetrahydropyridine (IV).The hydroboration of (IV) with NaBH4 and BF3 ethearate in dimethoxyethane affords trans-1-benzyl-4-(2-methoxyphenyl)piperidin-3-ol (V),which is treated with BBr3 in dichloromethane to give the 4-hydroxyphenyl derivative (VI).The hydrogenolysis of (VI) with H2 over Pd/C in methanol yields trans-4-(2-hydroxyphenyl)piperidin-3-ol (VII),which is treated with tert-butoxycarbonyl anhydride and triethylamine in DMF to afford the carbamate (VIII).The condensation of 3-chloropropyl-(2-methoxyphenyl)ether (IX) (obtained by the NaH promoted condensation of 2-methoxybenzyl chloride (X) and 3-chloropropanol (XI)) with (VIII) by means of K2CO3 in hot 2-butanone gives the expected phenolic ether (XII),which is condensed with 7-(bromomethyl)quinoline (XIII) by means of NaH in DMF yielding the piperidinyl ether (XIV).The selective hydrogenation of (XIV) with NiCl2 and NaBH4 in methanol affords the tetrahydroquinoline derivative (XV),which is finally treated with HCl in methanol to eliminate the carbamate protecting group.