Sch-69956 [(-)-(S)-isomer], Sch-69955 [(+)-(R)-isomer], Sch-54429
Chemical Name: (?-8-Chloro-11-[4-[2-(4-pyridyl)acetyl]piperazin-1-yl]-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
CAS No. 169250-83-3
项目整合开发状态: Preclinical
项目研究机构: Schering-Plough (Originator)
合成路线:Ketone (I) was reduced with sodium borohydride in methanol to alcohol (II),which was then converted into chloride (III) on treatment with thionyl chloride in cooled toluene.Alkylation of piperazine (IV) with chloride (III) in the presence of triethylamine gave V.Finally,piperazine (V) was condensed with 4-pyridylacetic acid (VI) in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (DEC),1-hydroxybenzotriazole (HOBt),and N-methylmorpholine in DMF to afford the target amide.
合成路线:Treatment of propargyl alcohol (I) with two equivalents of butyllithium in THF,followed by chlorotrimethylsilane,and then with methanol and a catalytic amount of distannoxane,gave 3-(trimethylsilyl)-2-propyn-1-ol (II).Partial reduction of acetylenic triple bond with sodium bis(2-methoxyethoxy)aluminum hydride afforded the expected (E)-olefin (III),which on treatment with methanesulfonyl chloride and triethylamine in dichloromethane provided mesylate (IV).Finally,alkylation of 1-deoxynojirimycin (V) with mesylate (IV) in the presence of triethylamine gave the title compound.
📌 参考资料/链接：
参考文献标题:Novel nojirimycin derivs.
文献作者:Lesur,B.; Ducep,J.-B.; Danzin,C.(Merrell Pharmaceuticals,Inc.)
参考来源:EP 0453692; EP 0454580; JP 1993086072; US 5252587; US 5536732
📄 详细内容
合成路线:Ketone (I) was reduced with sodium borohydride in methanol to alcohol (II),which was then converted into chloride (III) on treatment with thionyl chloride in cooled toluene.Alkylation of piperazine (IV) with chloride (III) in the presence of triethylamine gave V.Finally,piperazine (V) was condensed with 4-pyridylacetic acid (VI) in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (DEC),1-hydroxybenzotriazole (HOBt),and N-methylmorpholine in DMF to afford the target amide.
合成路线:Treatment of propargyl alcohol (I) with two equivalents of butyllithium in THF,followed by chlorotrimethylsilane,and then with methanol and a catalytic amount of distannoxane,gave 3-(trimethylsilyl)-2-propyn-1-ol (II).Partial reduction of acetylenic triple bond with sodium bis(2-methoxyethoxy)aluminum hydride afforded the expected (E)-olefin (III),which on treatment with methanesulfonyl chloride and triethylamine in dichloromethane provided mesylate (IV).Finally,alkylation of 1-deoxynojirimycin (V) with mesylate (IV) in the presence of triethylamine gave the title compound.
参考文献标题:New deoxynojirimycin derivatives as potent inhibitors of intestinal alpha-glucohydrolases
文献作者:Lesur,B.; et al.
参考来源:Bioorg Med Chem Lett 1997,7(3),355-360