Lonapalene, RS-43179
氯萘帕林Chemical Name: 1,4-Diacetoxy-6-chloro-2,3-dimethoxynaphthalene
CAS No. 91431-42-4
项目整合开发状态: Phase III
项目研究机构: Roche Bioscience (Originator), AstraZeneca (Licensee)
合成路线:The chlorination of 6-choro-1,4-naphthoquinone (I) with Cl2 in acetic acid gives 2,3,6-trichloro-2,3-dihydro-1,4-naphthoquinone (II),which is treated with sodium acetate and Cl2 in refluxing acetic acid yielding 2,3,6-trichloro-1,4-naphthoquinone (II) The reaction of (III) with sodium methoxide in reftuxing methanol affords 6-chloro-2,3-dimethoxy-1-4-naphthoquinone (IV),which is finally reduced with H2 over Pd/C IP THF,and acetylated with acetic anhydride in pyridine (I).
📌 参考资料/链接：
参考文献标题:1,4-Acyloxynaphthalene derivs.,topical compsns.containing them,methods for their preparation,and intermediates therefor
文献作者:Jones,G.H.; Venuti,M.C.; Young,J.M.(Syntex (USA),Inc.)
参考来源:EP 0107512; US 4466981
📄 详细内容
合成路线:The chlorination of 6-choro-1,4-naphthoquinone (I) with Cl2 in acetic acid gives 2,3,6-trichloro-2,3-dihydro-1,4-naphthoquinone (II),which is treated with sodium acetate and Cl2 in refluxing acetic acid yielding 2,3,6-trichloro-1,4-naphthoquinone (II) The reaction of (III) with sodium methoxide in reftuxing methanol affords 6-chloro-2,3-dimethoxy-1-4-naphthoquinone (IV),which is finally reduced with H2 over Pd/C IP THF,and acetylated with acetic anhydride in pyridine (I).
参考文献标题:RS-43179
文献作者:Castar,J.; Prous,J.
参考来源:Drugs Fut 1986,11(1),34
合成路线:The metalation of 4-chlorobromobenzene (I) with lithium gives 4-chlorophenyllithium (II),which is condensed with dimethyl squarate (III) in THF at -78 C giving 4-(4-chlorophenyl)-4-hydroxy-2,3-dimethoxy-2-cyclobuten-1-one (IV).The isomerization of (IV) in refluxing xylene (38 C) affords naphthohydroquinone (VI) through the intermediate ketene (V).Finally,compound (VI) is acetylated with acetic anhydride in pyridine - dimethylaminopyridine.
参考文献标题:Synthesis of lonapalene
文献作者:Perri,S.T.; Moore,H.W.
参考来源:Tetrahedron Lett 1987,28(39),4507-10
产品链接: CAS No. 91431-42-4››