新产品编号:739303
Chemical Name: 2,3-Dimethoxy-6-[4-[4-(trifluoromethyl)phenoxy]piperidin-1-ylsulfonyl]benzohydroxamic acid
CAS No. 279221-23-7
项目整合开发状态: Preclinical
项目研究机构: Pfizer (Originator)
合成路线:Coupling between N-Boc-4-piperidinol (I) and 4-fluorobenzotrifluoride (II) in the presence of cesium carbonate afforded ether (III).Subsequent acidic cleavage of the Boc protecting group of (III) furnished piperidine (IV) (1).Acylation of piperidine (IV) with 3,4-dimethoxybenzenesulfonyl chloride (V) yielded the corresponding sulfonamide (VI).Regioselective metalation of (VI) by means of tert-butyllithium,followed by quenching with dry carbon dioxide gave rise to the carboxylic acid (VII).This was converted to the corresponding acid chloride (VIII) employing oxalyl chloride,and then condensed with O-tetrahydropyranylhydroxylamine (IX).The resultant tetrahydropyranyl-protected hydroxamate (X) was finally deprotected by treatment with an in situ generated solution of methanolic HCl.
📌 参考资料/链接：
参考文献标题:Hydroxamic acid derivs.as matrix metalloprotease inhibitors
文献作者:Villamil,C.I.; Becker,D.P.; Bedell,L.J.; Freskos,J.N.; Rao,S.N.; Getman,D.P.; Decrescenzo,G.A.; Mischke,B.V.; Barta,T.E.; McDonald,J.J.(Pharmacia Corp.)
参考来源:EP 1177173; WO 0069819
📄 详细内容
合成路线:Coupling between N-Boc-4-piperidinol (I) and 4-fluorobenzotrifluoride (II) in the presence of cesium carbonate afforded ether (III).Subsequent acidic cleavage of the Boc protecting group of (III) furnished piperidine (IV) (1).Acylation of piperidine (IV) with 3,4-dimethoxybenzenesulfonyl chloride (V) yielded the corresponding sulfonamide (VI).Regioselective metalation of (VI) by means of tert-butyllithium,followed by quenching with dry carbon dioxide gave rise to the carboxylic acid (VII).This was converted to the corresponding acid chloride (VIII) employing oxalyl chloride,and then condensed with O-tetrahydropyranylhydroxylamine (IX).The resultant tetrahydropyranyl-protected hydroxamate (X) was finally deprotected by treatment with an in situ generated solution of methanolic HCl.
参考文献标题:Selective,orally active MMP inhibitor with an aryl backbone
文献作者:Barta,T.E.; Becker,D.P.; Bedel,L.J.; De Crescenzo,G.A.; McDonald,J.J.; Mehta,P.; Munie,G.E.; Villamil,C.I.
参考来源:Bioorg Med Chem Lett 2001,11(18),2481