Tenoxicam, Ro-120068, Liman, Tilcotil
替诺昔康Chemical Name: 4-Hydroxy-2-methyl-N-(2-pyridyl)-2H-thieno[2,3-e]-1,2-thiazine-3-carboxamide 1,1-dioxide
CAS No. 59804-37-4
项目整合开发状态: Launched-1987
项目研究机构: Kali-Chemie (Originator), Roche (Originator)
合成路线:The reaction of methyl 3-hydroxythiophene-2-carboxylate (I) with PCl5 in refluxing CCl4 gives 3-chlorothiophene-2-carboxylic acid (II),which by treatment with NaHSO3 and Cu in basic water at 143 C in a pressure vessel is converted into 3-sulfothiophene-2-carboxylic acid (III).The esterification of (III) with refluxing methanol affords methyl 3-sulfothiophene-2-carboxylate (IV),which by reaction with refluxing SOCl2 yields methyl-3-chlorosulfonylthiophene-2-carboxylate (V).The condensation of (V) with sarcosine ethyl ester (VI) in hot CHCl3 gives methyl-3-(N-ethoxycarbonyl-methyl-N-methylsulfamoyl)thiophene-2-carboxylate (VII),which is cyclized by treatment with sodium methoxide in refluxing methanol affording 3-ethoxycarbonyl-4-hydroxy-2-methyl-2H-thieno-[2,3-e]-1,2-thiazine-1,1-dioxide (VIII).Finally,this compound is condensed with 2-aminopyridine (IX) in refluxing toluene.
📌 参考资料/链接：
参考文献标题:Thienothaiazine derivatives
文献作者:Horomatka,O.; Binder,D.; Pfister,R.; Zeller,P.(F.Hoffmann-La Roche AG)
参考来源:DE 2537070; FR 2303803; JP 51048694; NL 7510057
📄 详细内容
合成路线:The reaction of methyl 3-hydroxythiophene-2-carboxylate (I) with PCl5 in refluxing CCl4 gives 3-chlorothiophene-2-carboxylic acid (II),which by treatment with NaHSO3 and Cu in basic water at 143 C in a pressure vessel is converted into 3-sulfothiophene-2-carboxylic acid (III).The esterification of (III) with refluxing methanol affords methyl 3-sulfothiophene-2-carboxylate (IV),which by reaction with refluxing SOCl2 yields methyl-3-chlorosulfonylthiophene-2-carboxylate (V).The condensation of (V) with sarcosine ethyl ester (VI) in hot CHCl3 gives methyl-3-(N-ethoxycarbonyl-methyl-N-methylsulfamoyl)thiophene-2-carboxylate (VII),which is cyclized by treatment with sodium methoxide in refluxing methanol affording 3-ethoxycarbonyl-4-hydroxy-2-methyl-2H-thieno-[2,3-e]-1,2-thiazine-1,1-dioxide (VIII).Finally,this compound is condensed with 2-aminopyridine (IX) in refluxing toluene.
参考文献标题:Tenoxicam
文献作者:Serradell,M.N.; Blancafort,P.; Castar,J.
参考来源:Drugs Fut 1982,7(7),493
产品链接: CAS No. 59804-37-4››