L-757464
Chemical Name: 5-Chloro-2-[4-[4-(2-oxo-2,3-dihydrobenzoxazol-3-yl)piperidin-1-yl]butyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide
CAS No. 173842-04-1
项目整合开发状态: Preclinical
项目研究机构: Merck & Co. (Originator)
合成路线:Ortho lithiation of sulfonamide (I) with n-butyllithium,followed by carbonation with CO2 afforded benzoic acid (II).Subsequent cyclization with PPA with concomitant elimination of the N-tert-butyl group provided the saccharin analogue (III).Alkylation of the sodium salt of (III) with 1,4-dibromobutane (IV) in DMF yielded bromide (V).The reductive alkylation of 2-aminophenol (VI) with 1-tert-butoxycarbonyl-4-piperidone (VII) in the presence of sodium tri(acetoxy)borohydride provided the aminopiperidine (VIII),which was cyclized with triphosgene to afford benzoxazolone (IX).Then,removal of the N-Boc protecting group provided piperidine (X),which was finally alkylated with bromide (V) in the presence of Et3N in DMF at 80 C to furnish the title compound.
📌 参考资料/链接：
参考文献标题:Design and synthesis of N-alkylated saccharins as selective alpha1-a adrenergic receptor antagonists
文献作者:Nerenberg,J.B.; Erb,J.M.; Thompson,W.J.; Lee,H.Y.; Guare,J.P.; Munson,P.M.; Bergman,J.M.; Huff,J.R.; Broten,T.P.; Chang,R.S.; Chen,T.B..; O'Malley,S.; Schorn,T.W.; Scott,A.L.
参考来源:Bioorg Med Chem Lett 1998,8(18),2467
📄 详细内容
合成路线:Ortho lithiation of sulfonamide (I) with n-butyllithium,followed by carbonation with CO2 afforded benzoic acid (II).Subsequent cyclization with PPA with concomitant elimination of the N-tert-butyl group provided the saccharin analogue (III).Alkylation of the sodium salt of (III) with 1,4-dibromobutane (IV) in DMF yielded bromide (V).The reductive alkylation of 2-aminophenol (VI) with 1-tert-butoxycarbonyl-4-piperidone (VII) in the presence of sodium tri(acetoxy)borohydride provided the aminopiperidine (VIII),which was cyclized with triphosgene to afford benzoxazolone (IX).Then,removal of the N-Boc protecting group provided piperidine (X),which was finally alkylated with bromide (V) in the presence of Et3N in DMF at 80 C to furnish the title compound.
参考文献标题:Preparation of substituted 1,2-benzoisothiazolin-3-one 3 1,1-dioxides (o-benzoic sulfimides)
文献作者:Lombardino,J.G.
参考来源:J Org Chem 1971,36(13),1843
产品链接: CAS No. 173842-04-1››