新产品编号:334311
Chemical Name: N,N-Dimethyl-N'-[1-(10H-pyrazino[2,3-b][1,4]benzothiazin-8-ylmethyl)piperidin-4-yl]sulfamide
CAS No. 203648-51-5
项目整合开发状态: Preclinical
项目研究机构: Eisai (Originator)
合成路线:Displacement of the chloride group of 4-chloro-3-nitrobenzoic acid (I) with sodium disulfide,followed by reduction of the disulfide and nitro groups with Sn/HCl yields 3-amino-4-mercaptobenzoic acid (II),which is further esterified to (III) with methanolic HCl.Condensation of (III) with 2,3-dichloropyrazine (IV) produces the pyrazinobenzothiazine compound (V).The ester group of (V) is then reduced to alcohol (VI) employing LiAlH4.Subsequent treatment of alcohol (VI) with methanesulfonyl chloride and pyridine leads to the benzyl chloride (VII).
合成路线:4-Amino-1-benzylpiperidine (VIII) is condensed with dimethylsulfamoyl chloride to give the sulfamide (IX).Subsequent benzyl group hydrogenolysis in (IX) over Pd/C provides the piperidine (X).Finally,alkylation of piperidine (X) with chloride (VII) yields the title compound.
📌 参考资料/链接：
参考文献标题:Benzopiperidine derivs.
文献作者:Kaneko,T.; Clark,R.; Ohi,N.; Ozaki,F.; Kawahara,T.; Kamada,A.; Okano,K.; Yokohama,H.; Muramoto,K.; Arai,T.; Ohkuro,M.; Takenaka,O.; Sonoda,J.(Eisai Co.,Ltd.)
参考来源:EP 0934941; WO 9806720
📄 详细内容
合成路线:Displacement of the chloride group of 4-chloro-3-nitrobenzoic acid (I) with sodium disulfide,followed by reduction of the disulfide and nitro groups with Sn/HCl yields 3-amino-4-mercaptobenzoic acid (II),which is further esterified to (III) with methanolic HCl.Condensation of (III) with 2,3-dichloropyrazine (IV) produces the pyrazinobenzothiazine compound (V).The ester group of (V) is then reduced to alcohol (VI) employing LiAlH4.Subsequent treatment of alcohol (VI) with methanesulfonyl chloride and pyridine leads to the benzyl chloride (VII).
合成路线:4-Amino-1-benzylpiperidine (VIII) is condensed with dimethylsulfamoyl chloride to give the sulfamide (IX).Subsequent benzyl group hydrogenolysis in (IX) over Pd/C provides the piperidine (X).Finally,alkylation of piperidine (X) with chloride (VII) yields the title compound.
参考文献标题:Inhibitors of adhesion molecules expression: The synthesis and pharmacological properties of 10H-pyrazino[2,3-b][1,4]benzothiazine derivatives
文献作者:Kaneko,T.; Clark,R.S.J.; Ohi,N.; Kawahara,T.; Akamatsu,H.; Ozaki,F.; Kamada,A.; Okano,K.; Yokohama,H.; Muramoto,K.; Ohkuro,M.; Takenaka,O.; Kobayashi,S.
参考来源:Chem Pharm Bull 2002,50(7),922