PNU-176665

合成路线:Diazotization of the known aniline (I),followed by Sandmeyer reaction with CuCN and KCN afforded nitrile (II).Addition of hydrogen sulfide to (II) in the presence of Et3N in hot DMF led to the thioamide (III).Subsequent alkylation of (III) with methyl triflate gave the intermediate thioimidate (IV),and a further treatment of (IV) with hydrogen sulfide and pyridine provided dithioester (V).Displacement of the methylthio group of (V) by hydrazine yielded thiohydrazide (VI).Finally,cyclization of (VI) to the target thiadiazole was achieved upon refluxing in formic acid.

合成路线:Diazotization of the known aniline (I),followed by Sandmeyer reaction with CuCN and KCN afforded nitrile (II).Addition of hydrogen sulfide to (II) in the presence of Et3N in hot DMF led to the thioamide (III).Subsequent alkylation of (III) with methyl triflate gave the intermediate thioimidate (IV),and a further treatment of (IV) with hydrogen sulfide and pyridine provided dithioester (V).Displacement of the methylthio group of (V) by hydrazine yielded thiohydrazide (VI).This was cyclized to the required thiadiazole (VII) upon treatment with 3-carbomethoxypropionyl chloride (A) in refluxing THF.Aminolysis of the ester group of (VII) with methanolic ammonia at 100 C in a sealed vessel provided amide (VIII).This was finally dehydrated to the title nitrile using trifluoroacetic anhydride and pyridine.

参考文献标题:Synthesis and antibacterial activity of azolylphenyl oxazolidinones having 1,3,4-thiadiazolyl C-rings
文献作者:Ford,C.W.; Gadwood,R.C.; Thomasco,L.M.; Weaver,E.A.Zurenko,G.E.
参考来源:39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999,San Francisco) 1999,Abst F571


合成路线:Diazotization of the known aniline (I),followed by Sandmeyer reaction with CuCN and KCN afforded nitrile (II).Addition of hydrogen sulfide to (II) in the presence of Et3N in hot DMF led to the thioamide (III).Subsequent alkylation of (III) with methyl triflate gave the intermediate thioimidate (IV),and a further treatment of (IV) with hydrogen sulfide and pyridine provided dithioester (V).Displacement of the methylthio group of (V) by hydrazine yielded thiohydrazide (VI).Finally,cyclization of (VI) to the target thiadiazole was achieved upon refluxing in formic acid.
参考文献标题:The synthesis and antibacterial activity of 1,3,4-thiadiazole phenyl oxazolidinone analogues
文献作者:Thomasco,L.M.; Gadwood,R.C.; Weaver,E.A.; Ochoada,J.M.; Ford,C.W.; Zurenko,G.E.; Hamel,E.; Stapert,D.; Moerman,J.K.; Schaadt,R.D.; Yagi,B.H.
参考来源:Bioorg Med Chem Lett 2003,13(23),4193