新产品编号:391263
Chemical Name: N-[2(S)-(3-Chlorophenyl)-4-[1-oxospiro[benzothiophene-3(2H),4'-piperidin]-1'-yl]butyl]-N-methylbenzenesulfonamide
CAS No. 209349-02-0
项目整合开发状态: Biological Testing
项目研究机构: Merck & Co. (Originator)
合成路线:Alkylation of 3-chlorophenylacetic acid (I) with allyl bromide (II) using lithium hexamethyldisilazide provided racemic (III),which was resolved by recrystallization of the corresponding diastereoisomeric salts with (S)-alpha-methylbenzylamine.The desired (S)-carboxylic acid (IV) was converted to acid chloride and then treated with methylamine yielding amide (V).Reduction of (V) with LiAlH4 gave amine (VI),which was acylated with benzenesulfonyl chloride to afford sulfonamide (VII).A two-step oxidation of the allyl group of (VII) with osmium tetroxide and N-methylmorpholine N-oxide,followed by sodium periodate cleavage of the resulting diol produced aldehyde (VIII).Reductive condensation of (VIII) with spiro piperidine (IX) using NaBH(OAc)3 furnished adduct (X).Final oxidation of the sulfide group of (X) with one equivalent of Oxone(r) afforded the title sulfoxide.
📌 参考资料/链接：
参考文献标题:Spiro-substd.azacycles as modulators of chemokine receptor activity
文献作者:Mills,S.G.; MacCoss,M.; Springer,M.S.(Merck & Co.,Inc.)
参考来源:US 5962462; WO 9825605
📄 详细内容
合成路线:Alkylation of 3-chlorophenylacetic acid (I) with allyl bromide (II) using lithium hexamethyldisilazide provided racemic (III),which was resolved by recrystallization of the corresponding diastereoisomeric salts with (S)-alpha-methylbenzylamine.The desired (S)-carboxylic acid (IV) was converted to acid chloride and then treated with methylamine yielding amide (V).Reduction of (V) with LiAlH4 gave amine (VI),which was acylated with benzenesulfonyl chloride to afford sulfonamide (VII).A two-step oxidation of the allyl group of (VII) with osmium tetroxide and N-methylmorpholine N-oxide,followed by sodium periodate cleavage of the resulting diol produced aldehyde (VIII).Reductive condensation of (VIII) with spiro piperidine (IX) using NaBH(OAc)3 furnished adduct (X).Final oxidation of the sulfide group of (X) with one equivalent of Oxone(r) afforded the title sulfoxide.
参考文献标题:Discovery of potent human CCR5 antagonists for the treatment of HIV-1 infection
文献作者:Meurer,L.C.; Oates,B.; Finke,P.E.; et al.
参考来源:219th ACS Natl Meet (March 26 2000,San Francisco) 2000,Abst MEDI 118