KCO-912

Chemical Name: (3S,4R)-3-Hydroxy-2,2-dimethyl-4-(2-oxopiperidin-1-yl)-N-phenyl-1-benzopyran-6-sulfonamide
CAS No. 185695-83-4
项目整合开发状态: Phase II
项目研究机构: Novartis (Originator)
合成路线:Lithiation of 6-bromo-2,2-dimethyl-2H-1-benzopyran (I),followed by treatment with sulfur dioxide,gave the sulfinic acid (II),which was subsequently chlorinated to sulfonyl chloride (III) employing SO2Cl2.Condensation of sulfonyl chloride (III) with aniline furnished the target N-phenyl sulfonamide (IV).

合成路线:In a different method,sodium 4-hydroxybenzenesulfonate (V) was converted to the sulfonyl chloride (VI) upon treatment with thionyl chloride in hot 1,2-dichloroethane.Reaction of acid chloride (VI) with aniline provided sulfonamide (VII).Alkylation of the phenolic hydroxyl group of (VII) with 3-chloro-3-methyl-1-butyne (VIII) in the presence of DBU and CuCl gave the propargyl ether (IX),which was then cyclized to benzopyran (IV) under Claisen rearrangement conditions.

合成路线:Asymmetric epoxidation of benzopyran (IV) using NaOCl in the presence of the chiral catalyst (S,S)-(+)-N,N'-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediaminomanganese (III) chloride produced the desired (S,S)-epoxide (X).The title compound was then obtained by oxirane ring opening in (X) with the lithium derivative of 2-piperidinone (XI) in hot THF.