L-768277
Chemical Name: 5-[4-(Methylsulfonyl)phenyl]-6-phenylthiazolo[3,2-b][1,2,4]triazole
CAS No. 180696-49-5
项目整合开发状态: Preclinical
项目研究机构: Merck Frosst (Originator)
合成路线:The Grignard condensation of N-methoxy-N-methylbenzamide (I) with 4-(methylsulfanyl)benzylmagnesium bromide (II) in THF gives the expected ketone (III),which is brominated with Br2 in CCl4 yielding the alpha-bromoketone (IV).The oxidation of the thioether group of (IV) with oxone (potassium peroxymonosulfate) in dichloromethane/methanol/tert-butanol/water affords the corresponding sulfone (V) (1),which is finally cyclocondesed with thiazol-2-amine (VI) in refluxing ethanol or isopentanol.
合成路线:The Grignard condensation of N-methoxy-N-methylbenzamide (I) with 4-(methylsulfanyl)benzylmagnesium bromide (II) in THF gives the expected ketone (III),which is brominated with Br2 in CCl4 yielding the alpha-bromoketone (IV).The oxidation of the thioether group of (IV) with oxone (potassium peroxymonosulfate) in dichloromethane/methanol/tert-butanol/water affords the corresponding sulfone (V) (1),which is condesed with 4H-1,2,4-triazole-3-thiol (VI) in refluxing ethanol to give 2-[4-(methylsulfonyl)phenyl]-1-phenyl-2-(4H-1,2,4-triazol-3-ylsulfanyl)ethanone (VII).Finally,this compound is cyclized with polyphosphoric acid (PPA) in refluxing xylene.
📌 参考资料/链接：
参考文献标题:Aryl substd.5,5 fused aromatic nitrogen cpds.as anti-inflammatory agents
文献作者:Gauthier,J.Y.; Lau,C.K.; Leblanc,Y.; Li,C.-S.; Roy,P.; Therien,M.; Wang,Z.(Merck Frosst Canada Inc.)
参考来源:EP 0802917; JP 1999501902; US 5552422; WO 9621667
📄 详细内容
合成路线:The Grignard condensation of N-methoxy-N-methylbenzamide (I) with 4-(methylsulfanyl)benzylmagnesium bromide (II) in THF gives the expected ketone (III),which is brominated with Br2 in CCl4 yielding the alpha-bromoketone (IV).The oxidation of the thioether group of (IV) with oxone (potassium peroxymonosulfate) in dichloromethane/methanol/tert-butanol/water affords the corresponding sulfone (V) (1),which is condesed with 4H-1,2,4-triazole-3-thiol (VI) in refluxing ethanol to give 2-[4-(methylsulfonyl)phenyl]-1-phenyl-2-(4H-1,2,4-triazol-3-ylsulfanyl)ethanone (VII).Finally,this compound is cyclized with polyphosphoric acid (PPA) in refluxing xylene.
参考文献标题:A new series of selective COX-2 inhibitors: 5,6-Diarylthiazolo[3,2-b][1,2,4]triazoles
文献作者:Roy,P.; et al.
参考来源:Bioorg Med Chem Lett 1997,7(1),57
合成路线:The Grignard condensation of N-methoxy-N-methylbenzamide (I) with 4-(methylsulfanyl)benzylmagnesium bromide (II) in THF gives the expected ketone (III),which is brominated with Br2 in CCl4 yielding the alpha-bromoketone (IV).The oxidation of the thioether group of (IV) with oxone (potassium peroxymonosulfate) in dichloromethane/methanol/tert-butanol/water affords the corresponding sulfone (V) (1),which is condesed with 4H-1,2,4-triazole-3-thiol (VI) in refluxing ethanol to give 2-[4-(methylsulfonyl)phenyl]-1-phenyl-2-(4H-1,2,4-triazol-3-ylsulfanyl)ethanone (VII).Finally,this compound is cyclized with polyphosphoric acid (PPA) in refluxing xylene.
参考文献标题:Synthesis and biological evaluation of 5,6-diarylimidazo[2.1-b]thiazole as selective COX-2 inhibitors
文献作者:Th閞ien,M.; et al.
参考来源:Bioorg Med Chem Lett 1997,7(1),47
合成路线:The Grignard condensation of N-methoxy-N-methylbenzamide (I) with 4-(methylsulfanyl)benzylmagnesium bromide (II) in THF gives the expected ketone (III),which is brominated with Br2 in CCl4 yielding the alpha-bromoketone (IV).The oxidation of the thioether group of (IV) with oxone (potassium peroxymonosulfate) in dichloromethane/methanol/tert-butanol/water affords the corresponding sulfone (V) (1),which is condesed with 4H-1,2,4-triazole-3-thiol (VI) in refluxing ethanol to give 2-[4-(methylsulfonyl)phenyl]-1-phenyl-2-(4H-1,2,4-triazol-3-ylsulfanyl)ethanone (VII).Finally,this compound is cyclized with polyphosphoric acid (PPA) in refluxing xylene.
参考文献标题:Characterization of the in vitro oxidative metabolites of the COX-2 selective inhibitor L-766,112
文献作者:Trimble,L.A.; et al.
参考来源:Bioorg Med Chem Lett 1997,7(1),53