Rupatadine fumarate, UR-12592 fumarate, Alergoliber, Rupafin
芦帕他定 8-氯-6,11-二氢-11-[1-[(5-甲基-3-吡啶基)甲基]-4-亚哌啶基]-5H-苯并[5,6]环戊烷[1,2-b]吡啶盐酸盐 Chemical Name: 8-Chloro-11-[1-[(5-methyl-3-pyridyl)methyl]piperidin-4-ylidene]-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine fumarate
CAS No. 158876-82-5 (free base), 156611-76-6 (triHCl)
项目整合开发状态: Launched-2003
项目研究机构: Uriach (Originator), Recordati (Licensee)
合成路线:The reaction of 2-cyano-3-methylpyridine (I) with H2SO4 in t-BuOH gives the N-tert-butylamide (II),which is treated with two equivalents of BuLi and the corresponding dianion alkylated with 3-chlorobenzyl chloride to afford amide (III).The treatment of (III) with POCl3 gives nitrile (IV),which is cyclized to ketone (V) by subsequent treatment with CF3SO3H and aqueous HCl.Reaction of ketone (V) with the Grignard derivative prepared from chloride (VI) affords alcohol (VII),which is finally dehydrated by H2SO4 to give UR-12592,as shown in Scheme 20491401a.
合成路线:The key intermediate (VI) is synthesized through the condensation of 5-methylnicotinic acid (VIII) with 4-hydroxypiperidine by means of DCC in DMF to give amide (IX),followed by reduction with POCl3 and NaBH4 to give the amino alcohol (X),which is treated with SOCl2.
📌 参考资料/链接：
参考文献标题:Rupatadine Fumarate
文献作者:Garc韆-Rafanell,J.
参考来源:Drugs Fut 1996,21(10),1032
📄 详细内容
合成路线:The reaction of 2-cyano-3-methylpyridine (I) with H2SO4 in t-BuOH gives the N-tert-butylamide (II),which is treated with two equivalents of BuLi and the corresponding dianion alkylated with 3-chlorobenzyl chloride to afford amide (III).The treatment of (III) with POCl3 gives nitrile (IV),which is cyclized to ketone (V) by subsequent treatment with CF3SO3H and aqueous HCl.Reaction of ketone (V) with the Grignard derivative prepared from chloride (VI) affords alcohol (VII),which is finally dehydrated by H2SO4 to give UR-12592,as shown in Scheme 20491401a.
合成路线:The key intermediate (VI) is synthesized through the condensation of 5-methylnicotinic acid (VIII) with 4-hydroxypiperidine by means of DCC in DMF to give amide (IX),followed by reduction with POCl3 and NaBH4 to give the amino alcohol (X),which is treated with SOCl2.
参考文献标题:Process for the preparation of 8-chloro-6,11-dihydro-11-[1-[(5-methyl-3-pyridinyl)methyl]-4-piperidinylidene]-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
文献作者:Carceller,E.; Jim閚ez,P.J.; Salas,J.(J.Uriach & C韆.,SA)
参考来源:ES 9602107
产品链接: CAS No. 158876-82-5›› 产品链接: CAS No.156611-76-6››