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Tazarotene, AGN-190168, Tazoral, Avage, Suretin, Tazorac, Zorac

他扎罗汀Chemical Name: 6-[2-(4,4-Dimethyl-3,4-dihydro-2H-1-benzothiopyran-6-yl)ethynyl]pyridine-3-carboxylic acid ethyl ester
CAS No. 118292-40-3
项目整合开发状态: Launched-1996
项目研究机构: Allergan (Originator), Bioglan (Licensee), 3M Pharmaceuticals (Comarketer), PediaMed (Comarketer)
合成路线:The condensation of thiophenol (II) with 3-methyl-2-butenyl bromide (I) by means of NaOH in refluxing acetone gives 3-methyl-2-butenyl(phenyl)sulfide (III),which is cyclized by means of P2O5 and H3PO4 in refluxing benzene to yield 4,4-dimethyl-3,4-dihydro-1H-1-benzothiopyran (IV).The acylation of (IV) with acetyl chloride catalyzed by SnCl4 in benzene affords the corresponding 6-acetyl derivative (V),which by dehydration with lithium diisopropylamide and diethyl chlorophosphate in THF is converted into 6-ethynyl-4,4-dimethyl-3,4-dihydro-2H-1-benzothiopyran (VI).Finally,this compound is condensed with ethyl 6-chloropyridine-3-carboxylate (VII) by means of butyllithium in THF.The ester (VII) is obtained by esterification of the corresponding acid (VIII) with ethanol by means of dicyclohexylcarbodiimide (DCC) and dimethylaminopyridine (DMAP).
📌 参考资料/链接:
参考文献标题:Disubstd.acetylenes bearing heteroaromatic and heterobicyclic groups having retinoid like activity
文献作者:Chandraratna,R.A.S.(Allergan,Inc.)
参考来源:EP 0284288; JP 88255277; JP 95324085

📄 详细内容


合成路线:The condensation of thiophenol (II) with 3-methyl-2-butenyl bromide (I) by means of NaOH in refluxing acetone gives 3-methyl-2-butenyl(phenyl)sulfide (III),which is cyclized by means of P2O5 and H3PO4 in refluxing benzene to yield 4,4-dimethyl-3,4-dihydro-1H-1-benzothiopyran (IV).The acylation of (IV) with acetyl chloride catalyzed by SnCl4 in benzene affords the corresponding 6-acetyl derivative (V),which by dehydration with lithium diisopropylamide and diethyl chlorophosphate in THF is converted into 6-ethynyl-4,4-dimethyl-3,4-dihydro-2H-1-benzothiopyran (VI).Finally,this compound is condensed with ethyl 6-chloropyridine-3-carboxylate (VII) by means of butyllithium in THF.The ester (VII) is obtained by esterification of the corresponding acid (VIII) with ethanol by means of dicyclohexylcarbodiimide (DCC) and dimethylaminopyridine (DMAP).

参考文献标题:Disubstd.acetylenes bearing heteroaromatic and heterobicyclic groups having retinoid like activity
文献作者:Chandraratna,R.A.S.(Allergan,Inc.)
参考来源:US 5089509


合成路线:The condensation of thiophenol (II) with 3-methyl-2-butenyl bromide (I) by means of NaOH in refluxing acetone gives 3-methyl-2-butenyl(phenyl)sulfide (III),which is cyclized by means of P2O5 and H3PO4 in refluxing benzene to yield 4,4-dimethyl-3,4-dihydro-1H-1-benzothiopyran (IV).The acylation of (IV) with acetyl chloride catalyzed by SnCl4 in benzene affords the corresponding 6-acetyl derivative (V),which by dehydration with lithium diisopropylamide and diethyl chlorophosphate in THF is converted into 6-ethynyl-4,4-dimethyl-3,4-dihydro-2H-1-benzothiopyran (VI).Finally,this compound is condensed with ethyl 6-chloropyridine-3-carboxylate (VII) by means of butyllithium in THF.The ester (VII) is obtained by esterification of the corresponding acid (VIII) with ethanol by means of dicyclohexylcarbodiimide (DCC) and dimethylaminopyridine (DMAP).

参考文献标题:Disubstd.acetylenes bearing heteroaromatic and heterobicyclic groups having retinoid like activity
文献作者:Chandraratna,R.A.(Allergan,Inc.)
参考来源:WO 9611686


合成路线:The condensation of thiophenol (II) with 3-methyl-2-butenyl bromide (I) by means of NaOH in refluxing acetone gives 3-methyl-2-butenyl(phenyl)sulfide (III),which is cyclized by means of P2O5 and H3PO4 in refluxing benzene to yield 4,4-dimethyl-3,4-dihydro-1H-1-benzothiopyran (IV).The acylation of (IV) with acetyl chloride catalyzed by SnCl4 in benzene affords the corresponding 6-acetyl derivative (V),which by dehydration with lithium diisopropylamide and diethyl chlorophosphate in THF is converted into 6-ethynyl-4,4-dimethyl-3,4-dihydro-2H-1-benzothiopyran (VI).Finally,this compound is condensed with ethyl 6-chloropyridine-3-carboxylate (VII) by means of butyllithium in THF.The ester (VII) is obtained by esterification of the corresponding acid (VIII) with ethanol by means of dicyclohexylcarbodiimide (DCC) and dimethylaminopyridine (DMAP).
参考文献标题:Tazarotene
文献作者:Ngo,J.; Leeson,P.A.; Castar,J.
参考来源:Drugs Fut 1997,22(3),249


产品链接: CAS No. 118292-40-3››