UR-8962
Chemical Name: 4-[4-(Methylsulfonyl)phenyl]-3-[6-(1-pyrrolidinyl)pyridin-3-yl]furan-2(5H)-one
CAS No. 372107-53-4
项目整合开发状态: Preclinical
项目研究机构: Uriach (Originator)
合成路线:6-Chloronicotinic acid (I) is converted to the corresponding acid chloride (II) employing either SOCl2 or PCl5/POCl3.Treatment of acid chloride (II) with EtOH and Et3N,followed by reduction of the resultant ethyl ester with LiAlH4,furnishes 6-chloro-3-pyridylmethanol (III).Alcohol (III) is alternatively prepared by NaBH4 reduction of acid chloride (II).Chlorination of (III) by using SOCl2 gives the chloromethyl pyridine (IV),and further chloride displacement with KCN leads to nitrile (V).Substitution of the remaining chloride group of (V) upon heating with pyrrolidine (VI) furnishes the pyrrolidinyl pyridine (VII).Then hydrolysis of the nitrile function of (VII) under acidic conditions provides carboxylic acid (VIII).Bromination of 4-(methylsulfonyl)acetophenone (IX) in the presence of AlCl3 produces the phenacyl bromide (X).Finally,condensation between acid (VIII) and bromo ketone (X) under basic conditions gives rise to the title diaryl furanone
📌 参考资料/链接：
参考文献标题:Novel heterocyclic cpds.with anti-inflammatory activity
文献作者:Almansa Rosales,C.; Gonzalez Gonzalez,C.; Torres Barreda,M.C.(J.Uriach & C韆.,SA)
参考来源:EP 1281709; ES 2166710; WO 0183475
📄 详细内容
合成路线:6-Chloronicotinic acid (I) is converted to the corresponding acid chloride (II) employing either SOCl2 or PCl5/POCl3.Treatment of acid chloride (II) with EtOH and Et3N,followed by reduction of the resultant ethyl ester with LiAlH4,furnishes 6-chloro-3-pyridylmethanol (III).Alcohol (III) is alternatively prepared by NaBH4 reduction of acid chloride (II).Chlorination of (III) by using SOCl2 gives the chloromethyl pyridine (IV),and further chloride displacement with KCN leads to nitrile (V).Substitution of the remaining chloride group of (V) upon heating with pyrrolidine (VI) furnishes the pyrrolidinyl pyridine (VII).Then hydrolysis of the nitrile function of (VII) under acidic conditions provides carboxylic acid (VIII).Bromination of 4-(methylsulfonyl)acetophenone (IX) in the presence of AlCl3 produces the phenacyl bromide (X).Finally,condensation between acid (VIII) and bromo ketone (X) under basic conditions gives rise to the title diaryl furanone
参考文献标题:Synthesis and SAR of 4-pyrrolidinylarylheterocycles as COX-2 selective inhibitors
文献作者:Almansa,C.; Alf髇,J.; Cavalcanti,F.L.; G髆ez,L.; Miralles,A.
参考来源:Drugs Fut 2002,27(Suppl.A),
产品链接: CAS No. 372107-53-4››